12405 results for ""non-traditional+communal+storytelling+approach"+novel+segment+noted+in+critical+commentary"

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• RNA-sequencing of human skin samples obtained from SSc patients and healthy controls.

  Patient information SSc patients were recruited at the Department of Rheumatology of the Leiden University Medical Center (Leiden, The Netherlands). All patients met the American Rheumatism Association classification criteria for SSc (Subcommittee for scleroderma criteria 1980), and were classified according to LeRoy and Medsger criteria as either limited or diffuse cutaneous disease (LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, Rowell N 1988). Institutional review board approval and written informed consent was obtained before patients entered this study. Two 4 mm skin biopsies were taken from a standardized location on the most proximal part of the lower arm, distal from the elbow. In 10 patients the skin biopsy came from a clinically affected area and in 4 patients the skin was locally unaffected. One sample was used for RNA sequencing and one sample was used for immunohistochemistry. Skin biopsies from healthy individuals were commercially sourced (Tissue Solutions, UK) and collected from donors undergoing skin resection surgery and after informed consent. To match the healthy skin with patients as much as possible, skin biopsies from healthy controls were also taken from a similar position (the under-arm (for 4 controls) and leg (for 2 controls)). Healthy skin donors were selected to match the age and sex of the SSc patient cohort. Biopsies from patients and controls were equally treated and were both stored at -80°C until RNA isolation was performed. RNA from frozen skin biopsies was isolated using RNeasy kit from fibrous tissue (Qiagen, the Netherlands). RNA quantity was determined by using SimplyNano 2000 and quality was assessed on Tapestation (Agilent, the Netherlands). All samples included in the study had a RIN score above 7.0. Transcriptome characterisation and analysis RNA sequencing was performed using polyA selection and a stranded protocol using Ion Torrent next generation sequencing technology (Service XS, The Netherlands). The Ion PI Template OT2 200 Kit v3 and Ion PI Sequencing 200 Kit v3 were used according to the manufacturer’s instructions. 20 samples were run on 11 PI chips. PI chip analyses, base calling and quality checks were performed using the Torrent Server Suite. An average of 42 million 100 bp reads was generated per sample. Following quality control, reads were aligned to the human genome (Homo sapiens GRh38.78) using Bowtie2 and STAR (Dobin et al. 2013; Langmead and Salzberg 2012). Reads were first aligned with STAR. For the unmapped reads from STAR, a second alignment step was performed using bowtie2 (local very sensitive options)

  Dataset EGAD00001003832

• UK Biobank whole cohort directly genotyped and imputed data (~500,000 participants)

  Genotype data is available for all 500,000 participants in the UK Biobank cohort. Genotyping has been performed using the Affymetrix UK BiLEVE Axiom array on an initial 50,000 participants and the remaining 450,000 participants have been genotyped using the Affymetrix UK Biobank Axiom® array. The two arrays are extremely similar (with over 95% common content).Quality control and imputation (to over 90 million SNPs, indels and large structural variants) has been performed by a collaborative group headed by the Wellcome Trust Centre for Human Genetics.The following data are available:* A clean set of QC’ed genotype calls* Confidence values that a genotype call is correct* Intensity data to generate cluster plots* Extensive QC information regarding SNPs and samples including SNP metrics, batch effects, population structure and relatedness* Imputed dataFor further information, please refer to the UK Biobank website

  Study EGAS00001002399

• 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

• Genomic Analysis of Low Grade B-Cell Lymphoma

  We included tumors from 64 newly diagnosed or untreated Low Grade B-Cell Lymphoma (LGBCL) patients, consisting of SMZL (n = 48), NMZL (n = 6), EMZL (n = 2), LPL (n = 5), and B-NOS (n = 3) in this study. Samples were selected from cases consented to the Molecular Epidemiology Resource (MER) of the University of Iowa and Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). RNA or DNA were extracted from 64 frozen LGBCLs tumors (with available matched germline DNA for N=61. For RNA sequencing, library preparation was done using the Illumina TruSeq RNA Exome Kit and sequenced with 100 nucleotide paired-end reads using the HiSeq 4000. For WES, library preparation was done using the Agilent SureSelect XT kit and sequenced with 100 nucleotide paired-end reads using the Illumina HiSeq 4000.

  Study phs002552

• Whole Genome Association Study of Bipolar Disorder

  The goal of the project is to identify genes that make individuals more susceptible to bipolar disorder (manic depressive illness) and to better understand the brain pathways involved in the disease. Dataset versioning Version 1: European-American (EA) ancestry only Version 2: Version 1 plus African-American (AA) ancestry Version 3: EA and AA samples plus updated diagnostic criteria Consent groups and participant set General research use (GRU): 1767 controls (1081 EA controls, 686 AA controls) This consent group includes all controls for the Bipolar study, which are a subset of controls for the Schizophrenia study (subset of Schizophrenia: GRU). Bipolar and related disorders (BARD): 841 cases (691 EA cases, 150 AA cases) This consent group includes a subset of the Bipolar cases. Bipolar disorder only (BDO): 653 cases (388 EA cases, 265 AA cases) This consent group includes a subset of the Bipolar cases.

  Study phs000017

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): NIH Digital Health Solutions for COVID-19: IBM Covid19 Contact Tracing and Data Exchange Tools

  The goal of this project is to develop both contact tracing and secure data exchange tools. The contact tracing solution securely combines data from a variety of sources (including manual self-report data and mobile device surveys) to enable tracing of contacts with individuals that have tested positive for COVID-19 or have been exposed to COVID-19. The data exchange solution is a secure mechanism that empowers users to control the data they share in the course of their return to work, including the ability to provide a verifiable health status claim. These tools are being used by an employer to evaluate the risk of allowing individuals to return to normal activities, and also the ability to trace user contact with individuals diagnosed with or suspected of having contracted COVID-19. DOI: https://rapids.ll.mit.edu/10.57895/h0an-m559

  Study phs002516

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): Covidseeker and COVID-19 Citizen Science: Leveraging Citizen Science and Real-Time Geospatial Temporal Mobile Data for Digital Contact Tracing and SARS-CoV-2 Hotspotting

  The Covidseeker and COVID-19 Citizen Science Study integrates a retrospectively-determined geolocation digital program into an established digital infrastructure housed within the NIH-funded Eureka platform to enroll SARS-CoV-2 positive and negative individuals. The solution also leverages the ongoing COVID-19 Citizen Science Study cohort both in-person and remotely to test and implement existing technology to enhance readily accessible contact tracing methods and identify “hot spots” of transmission of SARS-CoV-2. The tools are designed to alert users regarding overlap with SARS-CoV-2 infected individuals, identifying businesses that were visited by someone who later tested positive for COVID-19, and working with those businesses and public health departments on strategies to reduce the spread of the virus. DOI: https://rapids.ll.mit.edu/10.57895/me7r-vp06

  Study phs002519

• A phase II trial of the aurora kinase A inhibitor alisertib for patients with castration resistant and neuroendocrine prostate cancer: efficacy and biomarker evaluation

  Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. In this single arm, multi-institutional open label phase 2 clinical trial of alisertib, sixty men were treated with alisertib 50mg twice daily for 7 days every 21-days. Eligibility included metastatic prostate cancer and at least one: small cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; elevated serum neuroendocrine markers. The primary endpoint was six-month radiographic progression free survival. Pre-treatment biopsies were evaluated by whole exome and RNA-seq.

  Study phs001666

• Childhood Cancer Data Initiative (CCDI): OncoKids - NGS Panel for Pediatric Malignancies

  This study aimed to systematically collect clinical, registry and genomic data on pediatric cancer patients, and to contribute to the CCDI Pediatric Data Ecosystem. Clinical, treatment and outcome data on 1,039 pediatric cancer patients whose molecular profile was characterized on OncoKids gene panel at Children's Hospital Los Angeles was abstracted and harmonized for submission to the NCI’s Cancer Data Service. The OncoKids panel was designed to detect DNA mutations and amplification in almost 200 oncogenes and tumor suppressor genes, a limited number of pharmacogenomic targets and 1,700 disease-associated gene fusions at the RNA level. The panel encompasses the vast majority of FDA’s relevant pediatric molecular target list, as well as additional genes associated with ultra-rare pediatric tumors. The final data elements included DNA/RNA sequence data, OncoKids test results, clinical data on demographics, diagnosis, comorbidity and adverse events and treatment data.

  Study phs002518

• African American Breast Cancer GWAS

  The GWAS includes African American participants from 9 epidemiological studies of breast cancer, comprising a total of 3,153 cases and 2,831 controls (cases/controls: The Multiethnic Cohort Study (MEC), 734/1,003; The Los Angeles component of The Women's Contraceptive and Reproductive Experiences (CARE) Study, 380/224; The Women's Circle of Health Study (WCHS), 272/240; The San Francisco Bay Area Breast Cancer Study (SFBCS), 172/231; The Northern California Breast Cancer Family Registry (NC-BCFR), 440/53;The Carolina Breast Cancer Study (CBCS), 656/608; The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort, 64/133; The Nashville Breast Health Study (NBHS), 310/186; and, The Wake Forest University Breast Cancer Study (WFBC), 125/153). Quality control of the GWAS data and additional details can be found in Chen et al. Hum Genet. 2013 (PMID: 22923054)

  Study phs000851

• The Ultrasound Study of Tamoxifen

  The Ultrasound Study of Tamoxifen is a 12-month longitudinal study to describe volumetric breast density change over time among women with and without tamoxifen exposure. Women were enrolled at the Karmanos Cancer Institute and Henry Ford Health Systems in Detroit, Michigan between 2011-2014. Enrollment included women prescribed tamoxifen for clinical indication (n=82) and a comparison group of women frequency matched on age, race, and menopausal status (n=165). Whole breast ultrasound tomography (UST) scans were used to measure volume averaged sound speed (m/s) as a surrogate of volumetric breast density. Ultrasound tomography (UST) scans were completed at baseline prior to tamoxifen initiation and were repeated at 1-3 months, 4-6 months, and 12 months after tamoxifen initiation. For the comparison group, UST scans were completed at baseline and 12 months. Questionnaires were completed at each scan.

  Study phs003183

• Center for Common Disease Genomics (CCDG) - Cardiovascular: Cleveland Clinic Cohort

  The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex inherited diseases. This study contains variant calls derived from the whole genome sequence data of an early-onset coronary artery disease case-control cohort collected by the Cleveland Clinic. Case status was assigned based on the presence of myocardial infarction, coronary artery stenosis greater than 70% in at least one coronary artery, and/or revascularization (coronary angioplasty with or without stent placement or coronary artery bypass grafting) at an early age. For these samples, "early age" is defined as men 60 years of age or younger and women 70 years of age or younger.

  Study phs001871

• Molecular Basis of Neuroendocrine Prostate Cancer (Trento/Cornell/Broad 2015)

  A subset of advanced prostate cancers can progress from an androgen receptor (AR)-driven state to AR independence, often associated with low or absent AR expression and extensive neuroendocrine differentiation. Once neuroendocrine prostate cancer (NEPC) develops, patients typically demonstrate an aggressive clinical course and poor overall survival. Early diagnosis is important but remains challenging as the clinical and pathologic features associate with AR independence and NEPC are poorly defined. We performed whole exome sequencing of 114 metastatic tumors from 81 patients (35 with morphologic features of NEPC). Serial or synchronous samples were included to characterize heterogeneity and the transition from adenocarcinoma to NEPC. Computational analysis of clonality and allele specific quantification were performed using CLONET. Quantitative mRNA assessment including AR signaling genes and DNA methylation were evaluated in the context of genomic changes.

  Study phs000909

• NIDDK International IBD Genetics Consortium Repository Global Screening Array

  The purpose of this GWAS meta-analysis is to assess IBD risk alleles using data collected by members of the International IBD Genetics Consortium and their collaborators around the world. Data from over 30 cohorts have been identified and are being combined for analysis. Genotyping has been conducted using a variety of chips with most samples genotyped using GSAMD-24v1-0 or GSA-CHO-Custom. Individual level genotype data will be made available whenever possible (some groups are only able to provide summary statistics due to institutional and/or governmental restrictions on data sharing), together with information on sex, self-reported ancestry, IBD affection status and diagnosis. This first batch includes data from North American sites who are members of the NIDDK-funded IBD Genetics Consortium. Additional data will be provided in an update as soon as they have gone through the QC process.

  Study phs002336

• Yale Center for Mendelian Genomics (YCMG)

  From 2012-2021, Yale University was home to one of four national centers created by the National Institutes of Health (NIH) to study the genetics of rare inherited diseases. Researchers at Yale University, University of Washington, the Broad Institute and a center operated jointly by Baylor University and Johns Hopkins University analyzed the genomes of thousands of patients who suffer from more than 6,000 rare Mendelian disorders affecting more than 25 million individuals in United States. The Centers for Mendelian Genomics (CMG) applied next-generation sequencing and computational approaches to discover the genes and variants that underlie Mendelian disorders. The discovery of new genes that cause Mendelian conditions expanded our understanding about their biology to facilitate their diagnosis, and potentially indicate new treatments. The CMG provided free exome sequencing and analysis to collaborating investigators for qualified phenotypes.

  Study phs000744

• Single-Cell Multi-Omic Analysis of the Vestibular Schwannoma Ecosystem Uncovers a Nerve Injury-Like State

  Vestibular schwannomas are benign tumors that can lead to significant morbidity, including hearing loss, facial nerve paralysis and obstructive hydrocephalus. The genomic landscape of vestibular schwannomas is relatively bland and the molecular pathophysiology of vestibular schwannomas is poorly understood. Therefore, we performed single cell RNA sequencing on 15 sporadic vestibular schwannomas, with paired single cell ATAC sequencing (n = 6) and whole exome sequencing (n = 12) to perform a detailed characterization of the vestibular schwannoma tumor microenvironment at the transcriptional and epigenetic level. We validated our results by analyzing bulk RNA sequencing data from 22 newly sequenced vestibular schwannomas and 173 previously sequenced bulk RNA sequencing data from 195 vestibular schwannomas. Data available in dbGaP include whole exome sequencing of 12 tumors and matched blood samples. Matching single cell RNA sequencing and single cell ATAC sequencing data is available via NCBI GEO.

  Study phs003318

• The Role of ZEB2 during Human Neural Crest Cell Formation

  This study examined the role of ZEB2 during human neural crest cell formation. Human neural crest cells were differentiated from WiCell H1 human embryonic stem cells (WA01). Genome-wide transcriptional analysis (RNA-seq) was performed at day-3 and day-5 of human neural crest cell formation following siRNA knockdown of ZEB2 and using an N-terminal ZEB2 mutant H1 human embryonic stem cell line generated using CRISPR genome editing. RNA-seq was also performed on edited and unedited H1 human embryonic stem cells. ATAC-seq analysis was performed at day-3 and day-5 human neural crest differentiated from the N-terminal ZEB2 mutant embryonic stem cell line. Together, these data reveal the regulatory role of ZEB2 in the human neural crest gene regulatory network. We provide raw sequencing files for all RNA-seq and ATAC-seq samples.

  Study phs002701

• Sequencing Lymphoma

  This repository contains sequencing data to describe the genomic profiles of several B-cell lymphomas including follicular lymphoma and Hodgkin lymphoma. We have used several different high throughput sequencing technologies to interrogate genomic DNA and RNA from tumor cells obtained from lymph node biopsies and normal cells obtained from skin biopsies and peripheral blood mononuclear cells. A number of sequencing platforms for DNA, RNA, and protein were used to generate the data. These platforms include exome sequencing and a custom capture panel (NimbleGen) that targets 7.05 MB corresponding to the exons and splice sites of 1716 genes related to lymphoma biology (WUSM-LP). Other platforms include single-cell RNA-seq and Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq), which was used to describe transcriptional and proteomic changes in immune cell subsets within lymphoma patients pre- and post-therapy.

  Study phs001229

• Efficacy of Ustekinumab Followed by Abatacept for the Treatment of Psoriasis Vulgaris (PAUSE)

  Psoriasis is a chronic immune disease of the skin and joints that affects about 2% of the population. The most common form of psoriasis is plaque psoriasis, also called psoriasis vulgaris. A variety of drugs, including biologics, are available for treatment of moderate to severe psoriasis. When biologic agents are stopped, psoriasis can return (relapse) and often requires the biologic to be restarted and continued. No treatment program has been identified to prevent relapse of psoriasis. The study design has a lead-in period of weight-based ustekinumab treatment, with all participants receiving either 45 mg ustekinumab ( 100 kg) administered subcutaneously at weeks 0 and 4. At week 12, participants will be assessed for a Psoriasis Area and Severity Index (PASI) 75 response to ustekinumab. Participants who do not achieve a PASI 75 score will be discontinued from the investigation and permitted to seek standard therapy.

  Study phs003395

• Spatiotemporal immune atlas of the first clinical-grade gene-edited pig-to-human kidney xenotransplant

  Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

  Study EGAS50000000244

• CNS Embryonal tumors

  The dataset represents a total of 58 DNA samples from 16 male and 12 female pediatric patients affected with embryonal central nervous system tumors. The samples were subject to whole genome sequencing, WGS, [48 samples, (representing 12 male and 11 female individuals)] and whole exome sequencing, WES, [10 samples, (representing 4 male and 1 female individuals)]. One tumor tissue sample and one peripheral blood sample were analyzed from each of 26 patients, whereas two tumor tissue samples and one peripheral blood sample were analyzed from two patients. The WGS samples were sequenced 2x150 bp paired-end on an Illumina HiSeqX v2.5 instrument, and the WES samples were sequenced 2x100 bp paired-end on an Illumina HiSeq 2500 instrument. The FASTQ files generated were aligned to the human reference genome sequence GRCh38/hg38 using bwa-mem, with the ALT-aware option turned on. Sorting of reads and marking of PCR duplicates was performed with GATK. Base quality score recalibration and joint realignment of reads around insertions and deletions (indels) were conducted using GATK tools. The dataset consists of 58 files in the CRAM format (lossless compression) with a total file size of ~8,8 TB. All CRAM files but one, are derived from one sequence run and one sample. P4551_227N_P4552_112N is a CRAM file where 2 sequence runs (P4551_227N and P4552_112N) from peripheral blood samples from the same individual, P019, were aligned into one single CRAM file. Additional genomic and molecular data (FASTQ, BAM, IDAT, and VCF files) and limited clinical data can be requested by ethically approved projects conducting research in the field of pediatric cancer.

  Dataset EGAD50000000298

• Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED-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 determine the sensitivities and specificities of ventillation/perfusion (V/Q) lung scans for acute pulmonary embolism (PE).Participants: A total of 1487 participants were enrolled.Conclusions: Almost all participants with pulmonary embolism had abnormal scans of high, intermediate, or low probability, but so did most without pulmonary embolism. Only in a minority of participants did the clinical assessment combined with the V/Q scan interpretation improve the overall chance of reaching a correct diagnosis of acute PE. Although a high probability scan usually indicated the presence of PE, only a small number of participants with PE had a high probability scan. Reference: PIOPED Investigators, 1990, PMID: 2332918.

  Study phs004020

• End motifs analysis of circulating DNA from the plasma of patients with stage II-III breast cancer (n=50), stage I-III non-small cell lung cancer (n=56), metastatic colorectal cancer (mCRC) (n=15) and healthy individuals (n=37)..

  We have developed an algorithm designed to discriminate cancer patients and healthy individuals based on cirDNA fragment end motif analysis assisted by machine learning, using data obtained from shallow whole genome sequencing (a method we call EMA). We applied EMA to cirDNA from the plasma of patients with stage II-III breast cancer, stage I-III non-small cell lung cancer, and metastatic colorectal cancer (mCRC). CirDNA from 158 individuals was prepared following the conventional double-stranded DNA library preparation (DSP). We also performed a single-stranded DNA library preparation (SSP) using mCRC patients and healthy control cirDNA, which allowed us to make the first ever end motif analysis in the literature which compares the use of DSP and SSP.

  Study EGAS50000001319

• Whole genome sequencing data from tumor and normal samples

  Whole genome sequencing FASTQ files from tumor and normal samples from 202 patients. All experiments reported in this article were performed in the Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited laboratories at Personalis Inc., as guided by the Association for Molecular Pathology (AMP) and CAP’s joint recommendations52. Preferred input material consisting of FFPE slides (enabling H&E and macrodissection which is part of the standard NeXT Personal process) was not available for the majority (94%) of tumor samples. Most tumor samples (72%) were processed from FFPE curls, with the remaining processed from pre-extracted DNA and fresh frozen material. Where FFPE material on slide was available, tumor sections were macrodissected to increase tumor content, with a minimum allowable cellularity threshold of 20% determined by pathological review. The tumor cellularity threshold of 20% was chosen based on prior work demonstrating that no significant correlation is observed between tumor purity and assay limit of detection (LOD) at this threshold31. Genomic DNA was isolated from tumor and normal samples and WGS libraries prepared as previously described31. Genomic DNA was isolated from matched tumor and normal samples using the Qiagen AllPrep DNA/RNA FFPE Tissue Kit or the QIAamp DNA Mini Kit (QIAGEN, Germantown, MD, USA) using internally optimized workflows. WGS sequencing libraries were prepared with 120-500 ng of acoustically sheared genomic DNA (Covaris LLC, Woburn, MA, USA) using the KAPA HyperPrep Kit (Roche Sequencing Solutions, Pleasanton, CA, USA) and customized methods. Libraries were cleaned-up using AMPure XP beads and then quantified using the KAPA Library Quantification Kit (Roche Sequencing Solutions, Pleasanton, CA, USA), before being sequenced to 30X depth of coverage using a NovaSeq 6000 instrument (Illumina, San Diego, CA, USA).

  Dataset EGAD50000001909

• Identification of four new susceptibility loci for testicular germ cell tumour, including variants near GAB2, GSPT1 and ZFPM1

  Genome wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify further SNPs associated with TGCT we conducted a multistage GWAS with a combined dataset of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P = 1.5 x 10-9), 11q14.1 (rs7107174, GAB2, P = 9.7 x 10-11), 16p13.13 (rs4561483, GSPT1, P = 1.6 x 10-8) and 16q24.2 (rs55637647, ZFPM1, P = 3.4 x 10-9). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.

  Study EGAS00001001302

• Pangenomic classification of pituitary adenomas

  Pituitary neuroendocrine tumors (PitNETs) are common. They are classified in five main histological types: PitNETs of POU1F1 (Pit1) lineage -lactotroph, somatotroph and thyrotroph -, gonadotroph, and corticotroph PitNETs. Pituitary tumorigenesis is poorly understood. We report here a pangenomic characterization of 134 PitNETs from all types, based on exome, genome, transcriptome, miRnome and methylome. Pit1 lineage was associated with a specific epigenetic signature of diffuse DNA hypomethylation, and correlated with expression of Pit1 markers and chromosomal instability. 45% of somatotroph PitNETs showed GNAS mutations. GNAS-wild type somatotroph showed a distinct transcriptome profile, expressing gonadotroph transcription factor NR5A1 (SF1). Sparsely granulated somatotroph PitNETs was classified apart from somatotroph, owing to a thyrotroph transcriptome signature. 43% of corticotroph PitNETs showed USP8 mutations, sharing a low epithelial-mesenchimal transition (EMT) transcriptome signature. Silent corticotroph PitNETs showed a gonadotroph transcriptome signature evoking transdifferentiation, and lost somatostatin target SSTR5 expression.

  Study EGAS00001003642

• Colorectal advanced adenomas NKI-AvL TGO COCOS series

  Colorectal cancer (CRC) develops from normal epithelium, through a benign precursor lesion called adenoma, by accumulation of genetic alterations affecting oncogenes and tumour suppressor genes. About 5% of colorectal adenomas are estimated to progress to CRC. However, it is important to identify which adenomas actually carry a high-risk of progression, because these serve as intermediate endpoints for e.g. screening programs. In clinical practice, adenomas with a size of ≥10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high-risk, although solid evidence for this classification is lacking. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression.For this tissue dataset, we applied low-pass whole genome sequencing to 96 advanced adenomas. Advanced adenomas were classified as lesions with low-risk or high-risk of progression, according to the presence of specific DNA copy number changes (Carvalho et al, CancerPrevRes, 2018).

  Study EGAS00001002952

• Ongoing_mutagenesis_RNAseq

  One of the key questions to be explored is whether the biological processes generating specific mutational signatures continue to operate in the human cancer cell lines or simply reflect past mutagenic activity which is no longer operative. To address this question, we have extracted mutational signatures from 1,000 cancer cell lines of diverse cancer types. Several cell lines with mutational signatures of interest were selected, subcloned over a defined period of time and their genomes sequenced. The increased load of the mutations representative of a specific mutational signature within the genome of a subclone when compared to its parental clone was informative of the on-going mutational processes. To further study the recent observation that some of the clones belonging to a same cell line acquired differencet numbers of mutations over a set period of time, their RNA will be subjected to RNA-sequencing to study their differences.

  Study EGAS00001002364

• Evolutionary analysis of pancreatic cancer and coexistent precursor lesions using whole exome sequencing data

  Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. Further, the evolution of these lesions contextualizes the dynamics of advanced stage disease. We analyzed the somatic variants of co-existing pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to a pancreatic cancer. We also found that this multi-step progression generally spans many years. Our data suggest that independent, high-grade pancreatic lesions observed in a histologic cross section often represent a single neoplasm that can spread and colonize the ductal system, accumulating spatial and genetic divergence over time.

  Study EGAS00001002778

• Transcriptome sequencing of Gingivo-buccal Cancer : ICGC-India Project_YR03

  Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection. Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 12 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.

  Study EGAS00001002851

• GoDARTS T2D-GENES Exome Sequencing Study is a subset of the ~52,000 Type 2 diabetes exome sequencing project.

  The GoDARTS T2D-GENES Exome sequencing study is a subset of a larger Type 2 Diabetes Exome Sequencing project. This effort is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date and includes samples from: T2D-GENES, GoT2D, ESP, SIGMA T2D, LuCAMP, and ProDIGY. This data generated from the Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) cohort was part of the T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) consortium, which is a NIDDK-funded international research consortium that seeks to identify genetic variants for T2D through multiethnic sequencing studies. Sequencing for the GoDARTS study was performed at the Broad Institute using Illumina Rapid Capture on Illumina HiSeq machines.

  Study EGAS00001002937

• Single cell RNAseq of PBMC from bladder cancer patients

  Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had >80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.

  Study EGAS00001004008

• Genomic DNA of tumor tissues, adjacent normal tissues, and peripheral blood were extracted using QIAamp DNA mini Kit (QIAGEN, cat. #51306)

  Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single cell resolution. Using optimized single cell multiomics sequencing together with multiregional sampling of the primary tumor, lymphatic and distant metastases, we provide insights beyond intratumoral heterogeneity. Genome wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 sequenced patients. The cancer cells’ DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue, and those of repetitive element Long Interspersed Nuclear Element 1. Our work demonstrates the feasibility of reconstructing genetic lineages, and tracing their epigenomic and transcriptomic dynamics with single cell multiomics sequencing.

  Study EGAS00001003242

• Single cell RNAseq of PBMC from RCC patients

  Frozen PBMC samples containing at least 1 million cells were thawed for 1 minute at 37C and washed twice with RPMI complete media (10% FBS with glutamate and Pen/Strep). All of the samples had >80% viable cells. Sample processing for single-cell RNA-seq was done using Chromium Single Cell 3’ Library and Gel bead kit v2 (PN-120237) following manufacturer’s user guide (CG00052, 10x Genomics, Pleasanton, CA). The total cell density was used to impute the volume of single cell suspension needed in the reverse transcription (RT) master mix, aiming to achieve ~ 6,000 cells per sample. cDNAs and libraries were prepared following manufacturer’s user guide (10x Genomics). cDNA amplification and indexed libraries were prepared using 12 and 14 cycles of PCR, respectively. Libraries were profiled, quantified, and sequenced as 5’ single-cell gene expression libraries.

  Study EGAS00001004451

• Test Study for EGA using data from 1000 Genomes Project - Phase 3

  The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies...

  Study EGAS00001005042

• An exome sequencing approach to defining the genetic risk factors for Achilles tendinopathy

  Musculoskeletal soft tissue injuries are complex phenotypes. Case control association studies using the candidate gene approach have predominantly been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to define the genetic profile of these injuries using whole exome sequencing and a customized analysis pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. These results provide a proof of concept for the use of a customized pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries.

  Study EGAS00001003234

• Transcriptome sequencing of Gingivo-buccal Cancer : ICGC-India Project_Batch05

  Transcriptome Sequencing of Gingivo-buccal Cancer: ICGC-India ProjectAs a part of the ICGC, India has undertaken genomic studies on gingivobuccal cancer of the oral cavity, which is the most prevalent form of cancer among men in India. There are various known environmental (life-style) correlates of this cancer, the most important of which are tobacco chewing and HPV infection. Transcriptome sequencing of paired RNA samples – isolated from the tumor and adjacent normal tissues of 28 patients – have been performed. Detailed clinical characterization of the patients, collection of data on demographic and environmental exposures, and isolation of DNA samples from adjacent normal and tumor tissues collected from each patient are being done at the Advanced Centre for Research, Treatment and Education on Cancer, Mumbai. Sequencing is being performed at the National Institute of Biomedical Genomics, Kalyani.

  Study EGAS00001003285

• IYDP Indonesian Y chromosome Diversity Project

  Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 126 from Indonesian islands, first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, ongoing interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape of today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of past isolation, interaction and change in one of the world’s least understood regions.

  Study EGAS00001006028

• Identification of neoantigen from MSI-CRC patient derived organoids and its application for targeting by autologous T cells

  Targeting neoantigens expressed only by tumor cells enable tumor destruction without unexpected damages to healthy tissues. Here, we identified neoantigens from microsatellite instable (MSI) colorectal cancer (CRC) patient-derived organoids by genomics and immunopeptidomics approches. The neoantigens in this study were predicted from frame-shift mutation by whole-genome sequencing and confirmed its presentation on organoids surface class I HLA molecules by mass spectrometry. We utilized these neoantigens to isolate neoantigen-specific CD8 T cells from autologous PBMC, and proved tumor organoids killing ability of the CD8 T cells, whereas it did not attack normal organoids. This study provides a platform to identify neoantigen from patient-derived cancer organoids and a model to validate T cell recognition, which could be useful for adoptive CD8 T cell transfer treatment for MSI-CRC patient.

  Study EGAS00001006633

• DNA methylation-based classification of sinonasal tumors [Proteomics data]

  The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. The repository includes the raw mass spectrometry-based proteomics data

  Study EGAS00001006712

• DNA methylation-based classification of sinonasal tumors [DNA sequencing]

  The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent previously misclassified adenoid cystic carcinomas. This repository includes the results from DNA sequencing and mass spectrometry-based proteomics.

  Study EGAS00001006713

• Deregulation of FOXF1/FENDRR from t(14;16)(q32;q24) defines a subtype of high risk lineage ambiguous leukemia

  Despite great progress in understanding the genomic basis of immature T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL) and acute leukemias of ambiguous lineage (ALAL), there are still cases that lack defining genetic markers, complicating risk stratification and limiting targeted therapeutic options. Here, we describe a subtype of leukemia defined by the t(14;16)(q32;q24) translocation, which places the FOXF1 gene and its antisense long noncoding RNA gene FENDRR under the regulatory control of the BCL11B enhancer, leading to their ectopic transcriptional activation. Analysis of different high-throughput sequencing data, including WGS, RNA-seq, scDNA-seq, scRNA-seq, ChIP-seq, ATAC-seq, and HiChIP-seq, identified BCL11B-enhancer mediated deregulation of FOXF1/FENDRR as a hallmark of a subtype of high-risk lineage ambiguous leukemia that is potentially amenable to targeted therapeutic intervention.

  Study EGAS50000001255

• H3K27ac ChIP-seq in a selected group of AML patients

  ChIP-seq data were generated for a number of selected patients to investigate changes in enhancer and promoter regions. ChIP was performed as described previously with slight modifications27. Briefly, cells were crosslinked with 1% formaldehyde for 10 minutes at room temperature and the reaction was quenched with glycine at a final concentration of 0.125 M. Chromatin was sheared using the Covaris S220 focused-ultrasonicator to an average size of 250–350 bp. A total of 2.5 µg of antibody against H3K27ac (Abcam, ab4729) was added to sonicated chromatin of 2 × 106 cells and incubated overnight at 4 °C. Protein A sepharose beads (GE healthcare) were added to the ChIP reactions and incubated for 2 h at 4 °C. Beads were washed and chromatin was eluted. After crosslink reversal, RNase A and proteinase K treatment, DNA was extracted with the Monarch PCR & DNA Cleanup kit (NEB). Sequencing libraries were prepared with the NEBNext Ultra II DNA Library Prep Kit for Illumina (NEB) according to the manufacturer’s instructions. The quality of dsDNA libraries was analyzed using the High Sensitivity D1000 ScreenTape Kit (Agilent) and concentrations were assessed with the Qubit dsDNA HS Kit (Thermo Fisher Scientific). Libraries were single-end sequenced on a HiSeq 4000 (Illumina). ChIP-seq reads were aligned to the human reference genome build hg19 with bowtie

  Dataset EGAD00001007582

• Burden of DNMs in children born conceived using ART

  The dataset is composed by processed whole genome sequencing data generated from 53 children and their respective parents, forming 49 trios (mother, father and child) and 2 quartets (mother, father and two siblings). A total of 18 children were born after spontaneous conception (n = 18); 17 children were born after in vitro fertilization (IVF) and another 18 children were born after intracytoplasmic sperm injection combined with testicular sperm extraction (ICSI-TESE)

  Dataset EGAD00001008208

• WTS and WES of Renal Cell Carcinoma Tumors From a Phase III Anti-Angiogenic Adjuvant Therapy Trial

  Archival de-identified formalin-fixed paraffin-embedded RCC tumor tissue blocks from nephrectomy or tumor biopsy were processed as per below and the same sections were used for both DNA and RNA extractions. For WES (ACE version 3; Illumina NovaSeq), samples were profiled using Personalis ACE Cancer Exome (Personalis, Inc, Menlo Park, CA) Whole-transcriptome profiles were generated by RNA-seq (Accuracy and Content Enhanced (ACE) version 3; Illumina NovaSeq) using Personalis ACE Cancer Transcriptome (Personalis, Inc, Menlo Park, CA ) Of the 615 patients in the intent-to-treat population in S-TRAC trial, 193 individual specimens were available for molecular profiling, of which 171 (27.8%) (sunitinib, n = 91; placebo, n = 80) returned results for the WES analysis, and 133 (21.6%) (sunitinib, n = 72; placebo, n = 61) returned results for the GES analysis. Of the 138 WTS samples with data, replicates for two patients were summarized by median expression, and three samples were excluded from the final analysis due to low counts.

  Dataset EGAD00001009294

• Reference Epigenomes and Regulatory Landscape of CLL

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

  Dataset EGAD00001004046

• 13 WGS and 8 TCS data of ENKL patients treated with pembrolizumab.

  Whole-genome sequencing (WGS) was performed for 13 pairs of tumor-normal samples from patients diagnosed with NKTL. Genomic DNA from tumor tissue was extracted with QIAamp DNA Mini Kit. The DNA for the matching normal was obtained from blood or buccal swabs and purified by Blood and Cell Culture DNA Mini kit or E.Z.N.A. Tissue DNA Kit (Omega Bio-tek) according to manufacturer’s instructions. The quantity and quality were assessed by Quant-iT PicoGreen dsDNA Assay Kit (Invitrogen) and agarose gel electrophoresis. All sequencing libraries were prepared using TruSeq Nano DNA Library Prep Kit (Illumina). Paired-end sequencing was performed on Illumina HiSeq 2000 or HiSeq X Ten as 2x101 bp or 2x151 bp, respectively. 8 NKTL FFPE specimens were screened for somatic mutations using deep targeted capture sequencing (TCS). FFPE rolls or slides were extracted using QIAamp DNA FFPE Tissue kit (QIAGEN). The FFPE genomic DNA was treated with NEBNext FFPE DNA Repair Mix and assessed by Quant-it PicoGreen dsDNA Assay Kit (Invitrogen). The library was generated from 10-200 ng DNA with SureSelectXT Low Input Target Enrichment System for Illumina Paired-End Sequencing Library (Agilent Technologies) according to manufacturer’s instructions. RNA based probe was designed with SureDesign (Agilent Technologies) to target-capture 140 genes. Next, the captured libraries were pooled in equimolar concentration and sequenced on Illumina Novaseq 6000 platform with SP or S1 chip. Reads aligning to 40 selected genes were isolated post-alignment for this submission. Prefix used in filenames: T - Tumor samples N - Matched-Normal samples

  Dataset EGAD00001004140

• ChIIP-seq and RNA-seq

  epigenome profiling in tumor tissues and paired normal tissues of LUAD patients and transcriptome profiling in tumor tissues of LUAD patients.

  Dataset EGAD00001007066

• ATAC-Seq of healthy and IBD blood samples

  PBMCs from blood samples of 9 age- and gender-matched healthy subjects and 25 IBD patients were isolated through a Ficoll density gradient and used to isolate live CD4 T cells through a magnetic cell isolation kit (Miltenyi Biotec). Twelve thousand live CD4 T cells were then used to prepare ATAC-Seq libraries. Briefly, crude nuclei of live CD4+ T cells were treated with Tagment DNA buffer and Tagment DNA Enzyme (Nextera DNA Library Prep Kit, Illumina), and then the DNA was purified by MinElute PCR Purification Kit (Qiagen). Transposed DNA fragments were amplified using specific adapters followed by purification with MinElute PCR Purification Kit (Qiagen). Fragments from 240-360pb were selected in the PippinHT system (Sage Science). The quality of the library and its DNA concentration were assessed by Bioanalyzer instruments (Agilent Technologies) and ultimately submitted for sequencing using Illumina HiSeq 2500 sequencer, V4 chemistry.

  Study EGAS00001007343

• Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer

  Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor in adolescent and young adult patients. Currently, there is no standard-of-care treatment for these patients. Reliable models that represent this disease and can be used for translational research are scarce. To model SCCOHTs, we have established eight patient-derived tumoroid lines from tumor lesions of three patients with SCCOHT. The tumoroids recapitulate genomic and transcriptomic characteristics of the corresponding patient tumors and capture intrapatient tumor heterogeneity. Organoid drug profiling using a library of 153 clinical compounds identified methotrexate as an effective and selective drug against SCCOHTs with a clinically relevant IC50 of 35 nmol/L. RNA sequencing demonstrated that methotrexate induced TP53 pathway activation and apoptosis. These data underscore that organoid technology can support the design of therapeutic strategies for rare cancers.

  Study EGAS00001007911