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• Genome-wide DNA methylation profiles of NSCLC xenograft and primary lung tissues for the identification of epigenetic predictive biomarkers.

  Non-small cell lung cancers (NSCLC) are the most common cause of cancer-related deaths worldwide and primarily treated with platinum-based drugs like cisplatin and carboplatin, radiation and surgery. The major challenge in the management of NSCLC are intrinsic or acquired resistance mechanisms with only few published molecular markers which can predict the outcome of the patients. On the other side, changes in DNA methylation are observed in nearly all cancer types making them suitable as biomarker. Here genome-wide methylation profiles from MeDIP-Seq and gene expression profiling data of 22 primary NSCLC, adjacent normal tissue and PDX samples are provided. For each PDX tumor growth rates were measured in absence or presence of chemotherapy.

  Study EGAS00001002479

• Primary Cytotoxic T Cell Lymphomas Harbor Recurrent Targetable Alterations in the JAK-STAT Pathway

  Cytotoxic cutaneous T cell lymphomas (CTCLs) are uncommon but highly aggressive cancers of skin-homing cytotoxic T cells. These include the established World Health Organization (WHO) entity primary cutaneous gamma delta T cell lymphomas (PCGDTLs), the provisional WHO entity primary cutaneous CD8+ aggressive epidermotropic T cell lymphoma (PCAETCL), and samples that do not currently fit into a WHO category, referred to as cytotoxic CTCL-NOS (not otherwise specified). In this study, 35 CTCL cases were examined, and 9 PCAETCL cases were confirmed by CD8 expression and full-thickness epidermotropism. Whole genome sequencing (WGS) and bulk RNA sequencing were performed on these samples.  

  Study phs002499

• Genomic Landscape of Pediatric Germ Cell Tumors

  Germ cell tumors (GCTs) are cancers of the testis, ovary and extragonadal sites that occur in infants, children, adolescents, and adults. Post-pubertal (type II) malignant GCTs may present as a seminoma, non-seminoma or with mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratomas and (malignant) yolk sac tumors (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCTs in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years.

  Study phs002009

• Association of Oxidative Stress Pathway Alterations with Risk of Treatment Failure in RTOG9512: A Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord

  Based on the growing body of retrospectively collected and heterogeneously treated clinical cohorts and preclinical models, we investigated the clinical importance of NRF2 pathway alteration in an independent set of patients treated uniformly in the large prospective phase III trial RTOG 9512. We tested the hypothesis that patients with T2 glottic squamous cell carcinoma (SCC) harboring NRF2 pathway mutations would show radioresistance and have more local failure (LF) and locoregional failure (LRF) compared to those who did not have these mutations, using patients who received radiotherapy alone, thus removing potentially confounding effects of other therapies, like surgery or chemotherapy.

  Study phs003274

• Whole Exome Sequencing and RNA Sequencing of High Grade Serous Ovarian Cancer in Black and White Patients

  In this study, we generated new RNA and whole exome sequencing data from high-grade serous ovarian cancer tumor samples of self-identified Black and White individuals. Our RNA-Seq analysis revealed that, while the prevalence of subtypes varied across racial groups, the cluster-specific gene expression patterns were consistent. Despite these differences in subtype prevalence, the subtype-specific survival rates were similar across racial groups. Additionally, we used the WES-Seq data to characterize mutational signatures and their underlying causes in Black high-grade serous ovarian cancer (HGSC) cases, and compared the prevalence and distribution of these signatures with those in White TCGA cases.

  Study phs003632

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

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

  Study phs003938

• Whole exome sequencing of familial MDS, Two patients

  Although several causal genes of familial myelodysplastic syndromes (MDS) have been identified, the genetic landscape and the molecular pathogenesis are not totally understood. To explore novel driver genes and their pathogenetic significance, we performed whole exome sequence analysis of two individuals from a familial MDS pedigree and several candidate single-nucleotide variants were identified. Knockdown screening revealed that downregulation of a candidate gene enhanced colony forming capacity of primary murine bone marrow (BM) stem/progenitor cells. Our results indicate that a familial MDS-associated germline mutation in the candidate gene induces accumulation of DNA double-strand breaks, possibly through impaired PCNA polyubiquitination.

  Study JGAS000162

• Transcriptomic analysis of membranes from proliferative vitreoretinal diseases and isolated human retinal pigment epithelium

  This study investigates the transcriptomic profiles of proliferative vitreoretinal diseases (PVD) membranes, including proliferative vitreoretinopathy and epiretinal membranes collected from patients undergoing surgery, as well as human retinal pigment epithelial cells isolated from post-mortem donor eyes. Total RNA was extracted using AllPrep DNA/RNA Micro Kit (Qiagen) and cDNA libraries were prepared using the Ovation Solo RNA-seq Kit (Tecan). Multiplexed libraries were loaded onto a NovaSeq 6000 platform (Illumina), and sequences were generated using a 200-cycle kit. This study includes over 80 pathological and healthy samples to allow comparison of gene expression profiles and gain insights into the molecular mechanisms of PVD.

  Study EGAS50000001253

• Mongolia Western HCC

  Mongolia has the world’s highest incidence of hepatocellular carcinoma (HCC), with ~100 cases/105 inhabitants. We molecularly characterize the Mongolian (n=192) compared to Western HCCs (n=187) by RNA-seq and WES. Mongolian patients were predominantly younger, female, with HBV-HDV non-cirrhotic livers. Mongolian HCCs had higher rates of protein-coding mutations (121 vs 70 mut /tumor in West), and mutations in known (i.e. APOB) and putative HCC drivers (TSC2). A novel mutational signature (SBS Mongolia) was identified in 25% of cases associated with the carcinogenic DMS genotoxic signature. Two unique molecular classes enriched in HBV-HDV infection, female gender and inflamed tumors are described.

  Study EGAS00001005364

• PRADO trial - Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab plus nivolumab in stage III melanoma

  The PRADO trial tested a personalized response-directed treatment approach based on the pathologic response after neoadjuvant ipilimumab plus nivolumab in stage III melanoma patients. In patients achieving a major pathologic response, in their index lymph node (the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with partial response underwent TLND only, whereas patients with pathologic non-response underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Biomarker analyses based on baseline RNA sequencing data were performed in order to find features that are associated with major pathologic response.

  Study EGAS00001007601

• Fetal origins of malignant germ cell tumours

  Germ cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells (PGCs). They are uniquely able to generate embryonic and extraembryonic tissues, which in malignant GCTs carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood. Here, we studied the phylogenetic and transcriptional diversity of 15 malignant gonadal GCTs and four normal testis biopsies by sequencing 131 whole genomes and 416 transcriptomes from 14 gonadal histologies, excised by laser capture microdissection. Our findings demonstrate that tumours were initiated by whole genome duplication likely in embryogenesis, within ~5-8 cell divisions post-PGC specification, followed by chromosome 12p gains associated with invasive disease. Of note, 12p imbalances were not only generated through GCT-typical isochromosomes, but also through non-isochromosomic configurations. Whilst tumours developed along homogenous phylogenetic pathways, they spawned manifold tissues independent of genetic subclonal diversification. A key feature of GCT tissues was the expression of fetal-specific genes. The transcriptional diversity notwithstanding, we found universal transcriptional elements correlated with hallmark 12p gains. Overall, our study reveals stereotyped phylogenies and transcriptomes underpinning the development of GCT that originate in fetal life and may lend themselves to therapeutic manipulation.

  Dataset EGAD00001007038

• Single-cell transcriptomic analyses of peritoneal fluid from patients with colorectal cancer metastasized to the peritoneum

  The data published here contains single-cell RNA-sequencing (scRNAseq) data as obtained using the 3' scRNAseq using Chromium Single Cell 3’ Reagent from 10X Genomics on peritoneal fluid (PF) from patients with colorectal cancer (CRC) and peritoneal metastases (PM). Sequencing was performed in a paired-ended fashion on the NovaSeq6000.

  Dataset EGAD50000000248

• Swedish Bipolar Disorder exome sequencing (SWEBIC)

  This research project was a collaboration between the Karolinska Institute and the Stanley Center at the Broad Institute. In this project we sequenced and analyzed the whole exomes of 5340 SWEBIC Bipolar case samples from collaborators in Sweden. Genomic DNA from each samples was sequenced to a mean depth of 20x. The exome used Twist capture and samples were sequenced on Illumina HiSeqX machines producing CRAM files.

  Dataset EGAD50000001123

• Single-cell RNA-sequencing of CSF cells and PBMCs from individuals with neurological disorders

  We undertook single-cell RNA sequencing to establish gene expression and lymphocyte receptor sequences of CSF and peripheral blood leukocytes derived from patients with a variety of inflammatory, infectious and non-inflammatory neurological disorders. The aim of the study was the investigation of functional changes of the cells involved in neuroinflammatory responses.

  Dataset EGAD50000001173

• 10Xchromium 3' RNA-seq of 21 samples from human embryonic heart

  21 samples were taken from human embryonic heart of PCW 5.5-14 of a total of 13 fetuses. Samples were subject to 10Xgenomics chromium single cell 3' sequencing version 2 or 3. Data was analyzed using STARSolo version 2.7.10a, using human genome GRCh38.p12 and transcript annotations from ENSEMBL release 93 from reference package GRCh38-3.0.0 as available from 10Xgenomics.

  Dataset EGAD50000001499

• M116 DNA Methylation Array

  DNA samples were quantified with Qubit BR kit on a Qubit2.0 fluorimeter (ThermoFisher Scientific), and integrity was checked using agarose gel electrophoresis. DNA from samples passing the quality control was bisulfite-converted using the EZ DNA Methylation-Gold™ Kit (Zymo Research, Cat. D5005) following the manufacturer's instructions. Then, bisulfite-converted DNA was hybridized into the Methylation EPICv1.0 BeadChip (Illumina) array interrogating > 850,000 CpG sites according to manufacturer's instructions

  Dataset EGAD50000001678

• Whole exome sequence of human XXY fibroblasts

  This dataset contains Whole exome sequence generated using human skin fibroblast sample (ID 419281) from Klinefelter XXY syndrome patient fibroblasts. These fibroblasts were used to generate autosomally isogenic human iPSCs. The sample DNA was collected using commercial kit and Human All Exon v5 capture paired library was sequenced using Illumina HiSeq device. The fastq file (ID 493224) and analysis (ID 3209) bam files have been deposited.

  Dataset EGAD50000001362

• Transcriptome of periadrenal and subcutaneous fat in patients with hyperaldosteronism in comparison to patients with non-functional adenomas

  This study analyzed subcutaneous fat (SCF) and periadrenal fat (PAF) from patients with aldosterone-producing adenomas (APAs) and, as controls, non-functional adrenal adenomas (NFA) (SCF, n = 7; PAF, n = 5).

  Study EGAS50000001095

• Transcriptome data of periadrenal and subcutaneous fat in patients with hyperaldosteronism in comparison to patients with non-functional adenomas

  We analyzed subcutaneous adipose tissue (scAT) and periadrenal adipose tissue (paAT) from patients with Aldosterone-Producing Adenomas (APA) and, as controls, non-functional adrenal adenomas (NFA). RNA sequencing and immunohistochemistry of AT was performed (IHC, only on scAT). IHC markers included adipokines (leptin, adiponectin) and transcription factors (eg, c-jun, CaMKII)

  Dataset EGAD50000001590

• scRNAseq of fresh CRC punch biopsies

  The dataset includes single-cell RNAseq data generated by Plate-Seq technology from scDiscoveries. The dataset contains samples from a total of 5 different early CRC biobank patients (pt5, pt11, pt13, pt14, pt16) from 4 different sequencing runs. Punch biopsies of different regions of the tumor (Core, Invasive front and, if available, Adenoma) were FACS sorted onto plates prior to sequencing.

  Dataset EGAD50000002203

• G3BP2-KIT drives leukemia amenable to kinase inhibition in Ph-like ALL

  We describe a patient with Ph-like ALL, in which leukemic cells harbored an in-frame fusion between the GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2) and the KIT proto-oncogene.

  Study EGAS00001005181

• Whole exome sequencing data of Hispanic hepatocellular carcinoma

  The paired-end reads were aligned to the human reference genome (hg19) with decoy sequences (as used in the 1000 Genomes Project) using BWA (v0.7.5a) software. The duplicate reads were marked and subsequently removed using Picard (v1.140) (https://broadinstitute.github.io/picard/) and SAMtools (v0.1.19), respectively. Local realignment around insertions/deletions (indels) and base quality recalibration were performed using GATK (v3.6).

  Dataset EGAD00001011158

• Whole genome sequencing of HSPCs and pAML

  Whole genome sequencing data (Illumina HiSeq and NovaSeq) of clonal cultures derived from pediatric human bone marrow-derived hematopoietic stem and multipotent progenitor cells (in total 44 samples from 10 donors) and bulk pediatric acute myeloid leukemia blasts (in total 6 samples from 6 patients) to study the mutation accumulation.

  Dataset EGAD00001006338

• Hi-C in endometrial healthy and tumor tissues

  Hi-C libraries have been prepared by enzymatic digestion with MboI restriction enzyme and sonication. Illumina single-indexig primers have been use to amplify ligated fragments. Hi-C experiments have been performed on 10 slices (30um thick) of fresh-frozen tissues derived from 3 healthy and 3 tumor endometrial tissues of post-menopausal patients. Raw paired-end fastq.gz files are provided.

  Dataset EGAD00001010898

• V(D)J and 5' Gene Expression data on patients with aplastic anemia

  Chromium V(D)J and 5' Gene Expression platform (10X Genomics) was used to study patients with aplastic anemia. CD45+ cells from two patients (patient AA-3: 3 longitudinal samples from bone marrow and patient AA-4: 3 longitudinal samples from peripheral blood) were analysed. The raw data was processed using Cell Ranger 3.0.1 pipelines.

  Dataset EGAD00001006937