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• Mutational Signature and Transcriptomic Classification Analyses as the Decisive Diagnostic Tools for a Cancer of Unknown Primary with Neuroendocrine Differentiation

  PURPOSE: Cancer of unknown primary (CUP) is a group of metastatic tumors in which the standard diagnostic work-up fails to identify the site of origin of the tumor. The potential impact of precision oncology on this group of patients is large since their tumors might have actionable driver mutations that can provide treatment options otherwise not available for patients with these fatal cancers. This study investigated if comprehensive genomics analyses could inform on the origin of the tumor. PATIENT AND METHODS: Here we describe a patient whose tumor was misdiagnosed at least three times. Next-generation sequencing, a PDX mouse model and bioinformatics was used to identify an actionable mutation, predict resistance development to the targeted therapy, and to correctly diagnose the origin of the tumor. The Cancer Genome Atlas was used to benchmark the bioinformatics workflow. RESULTS: Despite the lack of a known primary tumor site and the absence of diagnostic immunohistochemical markers, the origin of the patient's tumor was established using the novel bioinformatics workflow. This included a mutational signature analysis of the sequenced metastases and comparison of their transcriptomic profiles to a pan-cancer panel of tumors from The Cancer Genome Atlas. We further discuss the strengths and limitations of the latter approaches in the context of three potentially incorrectly diagnosed TCGA lung tumors. CONCLUSION: Comprehensive genomics analyses could inform on the origin of tumors in patients suffering from CUP.

  Study EGAS00001003026

• Growth Hormone (GH) -secreting Pituitary Adenoma

  Data from 12 fresh-frozen somatotropinomas and their corresponding blood samples. Details are given in Valimaki et al. Whole-genome sequencing of Growth Hormone (GH) -secreting Pituitary Adenoma. Provisionally accepted, 2015.

  Study EGAS00001001293

• Dataset-linking-WGS-via-README-for-EGAS00001004884

  This dataset contains 139 Tumor and Control WGS files for samples for Gerhauser et al.,Cancer Cell, 2018, 34:996-1011. WGS and sequencing protocol was earlier described in Weischenfeldt et al, Cancer Cell, 2013.

  Dataset EGAD00001007669

• Chronic lymphocytic leukemia patient-derived xenografts recapitulate clonal evolution to Richter transformation

  Whole-genome sequencing (WGS) and RNA-seq data from patient-derived xenografts (PDXs) obtained from CLL and RT primary samples as described in Playa-Albinyana et al.

  Study EGAS00001006965

• NHLBI TOPMed: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE)

  ECLIPSE was a longitudinal observational study of 2164 COPD subjects and a smaller number of smoking controls (337) and nonsmoking controls (245) followed regularly for three years, with three chest CT scans (at baseline, one year, and three years) (Vestbo et al., 2008, PMID: 18216052). Subjects were enrolled at clinical centers in the US, Canada, Europe, and New Zealand. Inclusion criteria included subjects ages 40-75, at least 10 pack-years of smoking, and spirometry in GOLD grades 2-4 (COPD cases) or normal spirometry with post-bronchodilator FEV1 >85% (predicted) and FEV1/FVC>0.7 (controls). Study visits were performed at enrollment, three months, and every six months thereafter with spirometry, questionnaires, and other clinical evaluations. The ECLIPSE CT scans have been analyzed with the VIDA software for emphysema and airway phenotypes. ECLIPSE has provided key insights into the clinical epidemiology of COPD, including COPD exacerbations (Hurst, et. al., 2010, PMID: 20843247) and lung function decline in COPD (Vestbo, et. al., 2011, PMID: 21991892). ECLIPSE has been used in a number of genetic studies of COPD susceptibility and protein biomarkers (Faner, et. al., 2014, PMID: 24310110). Genome-wide gene expression microarray data are available in 147 induced sputum samples from COPD subjects and 248 peripheral blood samples from COPD and control subjects. Phenotype data for ECLIPSE subjects is available through dbGaP phs001252.

  Study phs001472

• Sci Trans Med - Mouliere et al. 2019

  Dac EGAC00001001570

• Liu et al 2020 Vietnamese study DAC

  Dac EGAC00001002551

• Mutation signatures in melanocytic nevi reveal characteristics of defective DNA repair

  Nevi are common benign melanocytic neoplasms that can be found on any skin location and share many of the genomic hallmarks of melanoma. In our recent report involving whole-exome sequencing of acquired nevi (Stark et al., 2018), ultra-violet radiation (UVR) related somatic mutation signatures (“signature 7”) (Alexandrov et al., 2013) were frequently observed in all lesions that were located on sun-exposed sites. In the study presented herein, we sought to investigate whether an independent Spanish cohort (Valencia, Spain) of minimally sun exposed nevi had genomic features consistent with our previous findings.

  Study EGAS00001004274

• Vitamin-D-Kids Asthma

  The Vitamin D Kids Asthma Study (VDKA) was a 48-week multicenter randomized, double-blinded, placebo-controlled trial of vitamin D3 for severe asthma exacerbations in children 6-16 years old, recruited from February 28, 2016 to September 20, 2019. An ancillary study for nasal sampling was conducted at the Pittsburgh site. Prior to randomization, participants completed questionnaires and underwent collection of nasal samples for gene expression studies. VDKA was approved by the IRBs of all participating institutions, and the ancillary study was approved by the IRB of the University of Pittsburgh. Written parental consent was obtained for participating children, from whom written assent was also obtained.

  Study phs004051

• Long-read single-cell RNA sequencing uncovers cell-type specific transcript regulation in COVID-19

  SARS-CoV-2 infection leads to extensive host transcriptomic changes, but the role of alternative splicing in shaping the immune response remains underexplored. Here, we present the first application of long-read single-cell RNA sequencing on nasopharyngeal swabs from COVID-19 patients and healthy controls to resolve transcript-level changes across cell types. Leveraging the strengths of long-read sequencing, we characterize alterations in both gene and isoform expression within cell populations of the upper respiratory tract—the primary site of SARS-CoV-2 entry. This approach provides new insights into how transcriptional regulation and splicing shape host immune responses to viral infection.

  Study EGAS50000001290

• Multi-modal spatial characterization of tumor-immune microenvironments in diffuse large B-cell lymphoma

  We have leveraged spatial transcriptomics together with proteomic and genomic analysis to investigate the spatial immunology and pathobiology of DLBCL. We define distinct cellular niches that differ in frequency across tumors, related to both Epstein-Barr virus (EBV) infection status and the anatomical site of the tumor, and show that residence within different cellular niches is associated with divergent functional states of T-cells and tumor B-cells due to different patterns of cell-cell communication. This provides a framework for understanding stereotyped patterns of spatial organization in DLBCL and immunological interactions associated with heterogeneity in immune cell infiltration and function across patients.

  Study EGAS50000001146

• He et al. RNA-seq data

  This dataset are the bam files of RNA-seq data from the paper by He et al.

  Dataset EGAD00001007135

• Sequencing data for oesophageal and related samples - Nowicki-Osuch, Zhuang et al (bulk RNA)

  Data supporting: “Deep molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition.” Nowicki-Osuch, Zhuang et al. RNAseq (BAM files) 241 tumour samples

  Dataset EGAD00001005388

• OSCC WES + WGS Boot et al. 2020

  Study EGAS00001004376

• Platelet DNA study Murphy et al 2023 DAC

  Dac EGAC00001003034

• Ewing's Sarcoma RNA-Seq

  28 Pretreated Ewing sarcoma tumor blood samples were collected from the Hospital for Sick Children (SickKids) and Mount Sinai Hospital in Toronto, Canada in accordance with each institution’s Research Ethical Board (REB) guidelines. Detailed clinical information (age at presentation, gender, tumor site, stage, etc.) were obtained from the corresponding institutional tumor banks. Transcriptome (RNA-Seq) sequencing was performed using established protocols on Illumina instruments.

  Dataset EGAD00001004188

• Thirant et al Nature Communications 2023 Data Access Commitee

  Dac EGAC00001003192

• DAC Bonaguro et al. 2021, STAT1 AM RNAseq

  Dac EGAC00001001963

• Kutanan and Liu et al 2021 Thai study DAC

  Dac EGAC00001002553

• Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Cohort Study

  The Emory University African American Microbiome in Pregnancy Cohort Study prospectively enrolls African American women between 18-40 years of age without chronic medical conditions into a longitudinal follow-up study that involves completing microbiome sampling and data collection at two time points in pregnancy (8-14 weeks gestation and 24-30 weeks gestation). The study is investigating the role of the oral, vaginal, and gut microbiome on preterm birth and other pregnancy outcomes as well as biobehavioral factors that shape the microbiome among this socio-demographically diverse group of women. Microbiome sampling involves the oral, vaginal, and gut sites. Biobehavioral factors that are being explored for their association with microbiome composition at the three body sites include measures of sociodemographic status as well as diet and nutrition, infectious and stress exposures.

  Study phs001865

• Longitudinal Study of Vaginal Flora

  This prospective observational study aims to advance our knowledge of the natural history and abnormal alteration in vaginal microbial flora, and to identify risk factors that are associated with these changes. A total of 5500 healthy, non-pregnant women of reproductive age will be enrolled and followed up in Birmingham, Alabama, for one year (baseline visit plus once every three months afterwards, totaling 5 visits). Detailed information on sociodemographic status, medical history, hygiene practice, sexual behavior and psychosocial stress will be collected through in-person interviews. Routine gynecological and dental examinations will be carried out during the study visits. Samples of vaginal secretion and blood will be collected. Laboratory tests to quantify vaginal microbial flora and to identify infection of bacterial vaginosis as well as common sexually transmitted diseases will be conducted. Future submissions may contain metadata or molecular data from additional subjects.

  Study phs002367

• Gut metagenome/FINRISK 2002 (Salosensaari et al. Nature Comms 2021)

  The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).

  Study EGAS00001005020

• Dopaminergic neuron differentiation of human embryonic stem cells

  2 replicates of dopaminergic neuron differentiation of human embryonic stem cells from timepoints day 17 and day 28, performed with 10X Genomics single cell RNA-seq. Part of the Ásgrimsdottir et al. (Arenas Lab).

  Study EGAS50000001099

• RNA-Seq data from 34 CAF-S3 subset in human breast and ovarian cancers

  This dataset is related to publications Costa et al. Cancer Cell 2018 and Givel et al. Nat. Commun. 2018 which describe the identification of 4 Cancer Associated Fibroblasts (CAF) in breast and ovarian cancer. This dataset contains transcriptomic profiles obtained by RNA-Seq of 34 CAF-S3 samples from breast and ovarian Tumors.

  Dataset EGAD00001004810

• RNA seq of MPNST tumour samples

  RNA sequencing of 10 MPNST tumour samples as part of a larger study of MPNST. Article: Lyskjær et al, 2020, J Pathol, "H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours".

  Study EGAS00001004528

• Healthy Never Smokers

  Bronchial brushing dataset from healthy never-smokers after exposure to diesel exhaust. Include 18 samples from 9 research participants who underwent bronchoscopy after controlled exposure to diesel exhaust. Main study design described in detail in Ryu et al 2022 AJRCCM (PMID: 35202552). This dataset was used in Hill et al Nature 2023.

  Dataset EGAD00001010024

• RNA-seq data of breast cancer HCI011 model from Ros et al (2020)

  RNA-seq data of the HCI011 and HCI011R models, GDC032 treated and control (total of 21 samples), from the paper: FOXM1 is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer that is detectable using metabolic imaging (Ros et al, 2020)

  Dataset EGAD00001006245

• Liu et al Taiwan genome-wide data DAC

  Dac EGAC00001003038

• Thirant, Peltier et al Data Access Commitee

  Dac EGAC00001001789

• Whole genome sequencing data of pediatric B-other subtype acute lymphoblastic leukemia

  For a long time, approximately 70% of childhood B-ALL cases could be classified routinely, and the remaining 30% were classified into the “B-other” group lacking the known genetic features. However, more recently, new genomic tools have uncovered new subtypes among the B-other groups. Approximately 10% of B-ALL cases lack the recurrent genetic abnormalities, and are referred as "B-other". They are typically more heterogeneous than other subtypes of B-ALL, and their prognoses are more variable. In a more recent update of the B-ALL classification, 27 subtypes were identified (Arber et al., 2022). The identification of some of these subtypes is dependent on NGS methods, such as RNA sequencing, which are not routinely used in all clinical laboratories. For example, ETV6::RUNX1-like and DUX4-rearranged subtypes have been identified using RNA sequencing. For this study, subtype predictions for some of the cases is acquired from ALLIUM (Krali et al., NPJ Precis Oncol., 2023) and ALLCatchR (Beder et al., Blood, 2022) based on the RNA-seq profiles.

  Study EGAS50000001497

• Quantitative analysis of a novel DNA hypermethylation panel using bronchial specimen for lung cancer diagnosis

  The dataset includes IDAT raw files for 10 samples and the analyzed DMP file which describes the differential methylation positions based on Illumina Infinium MethylationEPIC BeadChip. All samples (5 lung cancer cases vs. 5 benign lung disease controls) were obtained from bronchial washings at the site of the lesion under bronchoscopy manipulation. The histological type of the five lung cancer cases is adenocarcinoma and squamous cell carcinoma.

  Dataset EGAD00010002465

• RNAseq of 76 samples from Uveal Melanoma tumors

  Hotspot mutations in the spliceosome gene SF3B1 are reported in 20% of uveal melanomas. SF3B1 is involved in 3'-splice site (3'ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1 R625/K666 mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3'ss.

  Dataset EGAD00001004398

• Nasal MicroRNA during Bronchiolitis and Age 6y Asthma: MARC-35 Cohort

  We analyzed data from the 35th Multicenter Airway Research Collaboration (MARC-35) study to examine the relationship between nasal airway microRNAs (miRNAs) and the risk of developing childhood asthma. MARC-35 is a multicenter prospective cohort study which enrolled infants (age Structured interviews of the parents/guardians were performed by site investigators and clinical details were collected via emergency department and hospital inpatient chart reviews. Following the index hospitalization, trained study personnel conducted telephone interviews with parents/legal guardians at six-month intervals. Participants also underwent nasal swab sampling conducted by trained site personnel during the index bronchiolitis hospitalization and during an in-person follow-up examination at about age 6 years. Total RNA was extracted from nasal swab specimens using Trizol LS reagent (ThermoFisher Scientific, Waltham, MA) and the Direct-zol RNA Miniprep Kit (Zymo Research, Irvine, CA). Small RNA-seq was performed using the PerkinElmer NEXTFLEX® small RNA-seq v3 kit with Unique Dual Indexes (PerkinElmer, Waltham, MA) and sequenced on an Illumina NovaSeq6000 sequencer using an S2 50bp PE Flowcell (Illumina, San Diego, CA). Through dbGaP, limited de-identified phenotypic data (e.g., demographics) and RNA-seq FASTQ files will be made available. Among a cohort of infants hospitalized with bronchiolitis, we applied a small RNA sequencing approach and found miRNAs were associated with asthma risk factors, and highly expressed in lung tissue and immune cells (e.g., TH cells, neutrophils). They also played key roles in mechanisms relating to asthma, such as innate immunity, airway remodeling, and IgE regulation.

  Study phs003564

• Single Chromatin Fiber Profiling in the Human Brain

  We developed a human postmortem brain-applicable ‘Fiber-seq' protocol for genome-scale, PCR-free single molecule sequencing of on average 8-10kb long chromatin fibers, to map nucleosome positioning and nucleosome-depleted regions which include, for example, active promoters and enhancers. We generated two Fiber-seq reference sets, one from sorted non-neuronal NeuN- prefrontal cortex (PFC) nuclei from a 32 year old female donor, with total of 11,143,795 reads/fibers, and median of 30-fold genomic coverage. The other reference set was generated on sorted prefrontal NeuN+ neurons, from two 24 year old brain donors (1 female/1 male), with a combined total read/fiber count of 4,749,556 and median of 20-fold genomic coverage. Each of the peaks in the Fiber-seq libraries seq signal correlated with the ATAC peak levels in the neuronal and non-neuronal ATAC-seq libraries, respectively (promoters, clusters 1, 3; NeuN+, r = 0.574; NeuN-, r=0.683, PHowever, Fiber-seq detected 19,978 highly significant peaks which, while showing some non-significant/near-background ATAC-Seq alignments, lacked a corresponding site-specific enrichment in conventional short-read ATAC- and ChIP-seq datasets. However, 60% of these peaks were in repetitive DNA elements. Therefore, long read single chromatin fiber sequencing, which exceed the base pair length of conventional short-read libraries by two orders of magnitude, could capture many actively regulated repeat elements at the site of specific gene loci, that otherwise would remain unmappable by conventional ATAC-, and histone- ChiP-seq.

  Study phs003771

• Breast Cancer PDTX Encyclopaedia

  Molecular data from the collection of PDTX breast cancer models described in Bruna et al, 2016. Cell. It includes whole exome sequencing, shallow whole genome sequencing, expression arrays and reduced bisulfite representation sequencing (RRBS).

  Study EGAS00001001913

• ChIP-seq data of Hodgkin lymphoma cell line L-428

  ChIP-seq data (H3K4Me3, H3K27Ac histone modifications) of Hodgkin lymphoma cell line L-428. Samples were processed as previously described (Sud et al., 2018). The files are in bam format, aligned to build 37.

  Study EGAS00001003033

• Sequencing data for oesophageal and related samples - Black et al (WGS)

  Data supporting: "Understanding the malignant potential of gastric metaplasia of the oesophagus and its relevance to Barrett’s Oesophagus surveillance: individual-level data analysis" Black et al (WGS BOs/normals)

  Dataset EGAD00001011255

• Defective mitophagy and enhanced oxidative stress dictate regulatory T cell impairment in autoimmunity

  Regulatory T cell (Treg) impairment is a common denominator of autoimmune pathologies. Despite the extensive characterization of Treg cell phenotype in autoimmunity, the molecular mechanisms underlying their deterioration remain ill defined. To investigate Treg dysfunction during autoimmunity we performed transcriptomic analysis of CD4+CD25highCD127- Treg cells from peripheral blood of patients with autoimmunity.

  Study EGAS00001004470

• Coloured Project - Lankheet et al

  The data is for non-commercial use only.

  Dac EGAC50000000240

• Center for Common Disease Genomics [CCDG] - Cardiovascular: The Bangladesh Risk of Acute Vascular Events (BRAVE) Study

  The Bangladesh Risk of Acute Vascular Events (BRAVE) study is a hospital-based case-control study in Bangladesh which was established by the Cardiovascular Epidemiology Unit of Cambridge University in the UK in partnership with the key local cardiology and research centres to examine environmental, genetic, lifestyle and biochemical determinants of myocardial infarction (MI) among this South Asian population. By the end of 2016, this study has recruited ~8000 clinically confirmed first-ever MI cases (with a significant proportion being early-onset MI), and ~8000 healthy controls frequency-matched by age and sex. This site hosts data from ~500 whole genomes and ~1500 whole exomes (50% cases and 50% controls)

  Study phs001398

• Single Cell Analysis of Psoriasis Resolution following IL-23 Blockade

  Full-thickness skin biopsies were obtained from five individuals with severe psoriasis who were receiving risankizumab treatment. Skin biopsies were taken from lesional and non-lesional sites at baseline, and from lesional sites at day 3 and day 14 of therapy. All biopsies were taken from site-matched areas on the lower back/buttocks. Single-cell RNA sequencing was performed using a 10x Genomics platform. Myeloid and fibroblast populations showed the strongest change in gene expression after 3 days. An inflammatory, transient WNT5A+/IL24+ fibroblast state was identified, which was elevated in abundance in lesional skin versus non lesional skin, and decreased after 14 days of treatment. R1 and R2 FASTQs files are available.

  Study phs003351

• HIPO016 - glioblastoma tumour methylation microarray profiling

  Methylation microarray profiling (Illumina Human Methylation 450k and EPIC platforms) of 60 adult glioblastomas. Tumours were subtyped using the approach from Sturm et al. (https://doi.org/10.1016/j.ccr.2012.08.024): 12 IDH, 18 MES, 12 RTK I, 18 RTK II. DNA was prepared, assayed on the microarrays, and raw data computationally processed as described in Capper et al., "DNA methylation-based classification of central nervous system tumours": https://www.nature.com/articles/nature26000

  Dataset EGAD00010001797

• Large B cell lymphomas with CCND1 rearrangement have different immunoglobulin gene breakpoints and genomic profile than mantle cell lymphoma

  Next-generation sequencig data including whole-genome sequencing, whole-exome sequencing, and capture-based gene panels of large B cell lymphomas with CCND1 rearrangementas described in Özoğul,Montaner, Pol et al 2024.

  Study EGAS50000000564

• Analysis for oesophageal and related samples - Nowicki-Osuch, Zhuang et al (scRNA analysis)

  Data supporting: “Deep molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition.” Nowicki-Osuch, Zhuang et al. Single cell metadata and analysis 38 Barrett's and normals

  Dataset EGAD00001005455

• Sequencing data for oesophageal and related samples - Nowicki-Osuch, Zhuang et al (scRNA)

  Data supporting: “Deep molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition.” Nowicki-Osuch, Zhuang et al. scRNAseq (BAM files) 38 Barrett's and normal samples

  Dataset EGAD00001005438

• He et al. WES data

  This dataset are the bam files of WES data from the paper by He et al.

  Dataset EGAD00001007134

• Dataset-linking-WGS-samples-in-ega-box-81-via-README-for-study-EGAS00001002923

  This dataset contains 318 Tumor and Control WGS files submitted in another EGA box for samples for Gerhauser et al.,Cancer Cell, 2018, 34:996-1011. WGS and sequencing protocol was earlier described in Weischenfeldt et al, Cancer Cell, 2013.

  Dataset EGAD00001007861

• SJCRH Patient-derived orthotopic xenografts of pediatric brain tumors

  Primary patient pediatric brain tumors from patients treated at SJCRH were implanted and amplified only in the brain of immunocompromised mice without tissue culture steps and referred as patient-derived orthotopic xenografts (Smith et al, Acta Neuropathologica, 2020).

  Study EGAS00001005533

• Sequencing data for oesophageal and related samples - Linossi et al

  Data supporting: "Utility of ctDNA assessment after six weeks of immunotherapy to predict radiological response in advanced oesophageal cancer" Linossi et al

  Dataset EGAD00001015434

• Sequencing data for oesophageal and related samples - Nowicki-Osuch, Zhuang et al (scRNA)

  Data supporting: “Single-cell RNA sequencing unifies developmental programs of Esophageal and Gastric Intestinal Metaplasia.” Nowicki-Osuch, Zhuang et al. scRNAseq (FASTQ files) 59 samples

  Dataset EGAD00001010074