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• Tumor-derived exosomes modulate PD-L1 expression in monocytes

  In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell–derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples. Transfer of CLL-derived exosomes or hY4 alone to monocytes resulted in key CLL-associated phenotypes, including the release of cytokines, such as C-C motif chemokine ligand 2 (CCL2), CCL4, and interleukin-6, and the expression of PD-L1. These responses were abolished in Toll-like receptor 7 (TLR7)–deficient monocytes, suggesting exosomal hY4 as a driver of TLR7 signaling. Pharmacologic inhibition of endosomal TLR signaling resulted in a substantially reduced activation of monocytes in vitro and attenuated CLL development in vivo. Our results indicate that exosome-mediated transfer of noncoding RNAs to monocytes contributes to cancer-related inflammation and concurrent immune escape via PD-L1 expression.

  Study EGAS00001002377

• GEDI: A Developmental Model of Gene-Environment Interplay in SUDs: Combined Genotype Dataset from the "Great Smoky Mountains Study" and the "Caring for Children in the Community Study".

  1. Great Smoky Mountains Study (GSMS; Costello et al. 1996, 1997) Three cohorts of boys and girls, aged 9, 11, and 13 years at intake in 1993, were selected from a rural population of some 20,000 children using a household equal probability design. A two-phase procedure was used for White and African-American youth to increase power by oversampling children at risk for psychiatric and SUDs. Parents (usually mothers) of the first stage random population sample completed a questionnaire about their child's behavioral problems. Of 4,195 subjects selected, 95% (N=3,896) of parents completed the screen. All children scoring above a predetermined threshold (the top 25% of the total scores), plus a 10% random sample of the remaining 75%, were recruited for detailed interviews. Results can be back-weighted to population levels for analyses. Half of the sample consists of females, and 6% are African Americans, reflecting the population of the study area. The interviewed sample of white and African-American subjects was 1,070 (80% of those recruited). American Indian youth were oversampled (100%) because they are an understudied group known to be at high risk for stressful events, substance disorders, and mood disorders. Of 431 age-eligible children, 350 (81% boys, 49% girls) participated. Thus, the size of total GSMS sample is 1,070 + 350 = 1,420. Data collection is complete for ages 9-26, and age 30 interviews are in progress. By age 26 a total of 9,858 interviews had been completed; the average number of interviews per subject was seven, and by age 26, 97.3% completed two or more interviews. 2. The Caring for Children in the Community Study (CCC; Angold et al., 2002) This representative study of psychiatric illness and service use in African-American and White youth took place in four rural counties in the southeastern USA. The two-stage sampling design and methods are similar to those used in the GSMS. Of 4,500 youth randomly selected from the 17,117 9- to 17-year-olds in the public school's database, 3,613 (80.0%) were successfully contacted and agreed to complete the behavioral screen. Of the 1,302 selected to participate in the study, 920 (70.7%) interviews were completed. Because CCC was also the only study in GEDI to contain more than a very few African-American participants, these were omitted from the multi-site analyses. Reprinted with permission from Cambridge University Press from Costello et al., 2013: PMID: 23461817 References: Costello et al., 1996: PMID: 8956679 Costello et al., 1997: PMID: 9184514 Angold et al., 2002: PMID: 12365876

  Study phs000852

• Paired-end RNA-Seq Dataset of 72 Brain Organoid Samples: Sequencing and Gene Expression Analysis

  72 fastq sequencing files of 72 brain-organoid paired-end sequenced samples (R1/R2). RNA sequencing libraries were prepared using the NEBNext Ultra II RNA Library Prep Kit for Illumina following the manufacturer’s instructions (New England Biolabs, USA). mRNAs were first enriched with Oligo(dT) beads. The samples were sequenced using a 2x150 Pair-End configuration (ver. 1.5) on an Illumina NovaSeq 6000 The raw sequence reads were aligned to the human reference genome GRCh38 using the STAR aligner (Dobin et al., 2013). Gene expression levels were quantified using the FeatureCounts tool (Liao et al., 2014) (file: "All_Counts_final.xlsx") For more information, see "Study Description"

  Dataset EGAD50000000935

• Characterization of arrested B-lymphoid differentiation and leukemic cell states in ETV6-RUNX1-positive pediatric leukemia

  RNA was extracted from eight diagnostic ETV6-RUNX1 positive acute lymphoblastic leukemia samples collected in PAXgene blood RNA tubes using PAXgene Blood RNA kit (cat #762174, Qiagen GmbH, Hilden, Germany), following the version 2 instructions for manual purification. Samples were processed with Globin-Zero Gold rRNA Removal Kit (Illumina) and directional libraries were prepared using NEBNext Ultra Directional RNA Library Prep kit (New England Biolabs). The library preparation and paired end (150 bp) sequencing were performed by Novogene (HK) Company Limited (Hong Kong, China) using Illumina Novaseq 6000 aiming at 70 million read pairs per sample.

  Dataset EGAD00001006406

• RNASeq of bone marrow endothelial cells upon regeneration, (fetal) niche formation, and steady-state.

  Comprehensive transcriptional characterization of bone marrow endothelial cells by RNA sequencing was performed to determine the molecular properties/signatures of endothelium during bone marrow recovery and niche formation. Regenerative bone marrow endothelium was FACS-isolated from bone marrow aspirates of Acute Myeloid Leukemia patients 17 days after receiving chemotherapy (n=3). Niche-forming endothelial cells were FACS-isolated from fetal bones (gestational age 15-20 weeks) (n=3). Healthy adult bone marrow endothelial cells (n=7) were used as steady-state controls. cDNA was prepared using the SMARTer procedure (SMARTer Ultra Low RNA Kit, Clonetech). The provided file type is FASTQ.

  Dataset EGAD00001003904

• DNA methylation database for gynecological cancer detection, classification and assay development

  MeD-seq data (fastq files) from gynecological cancers and associated healthy tissues. In total 292 fastq files generated by MeD-seq are deposited consisting of: healthy tissues (vulva n=11, cervix n=15, endometrium n=13, fallopian tube n=18 and ovary n=13), precursor lesions of cancer (vulva n=23 and cervix n=46) and cancer (vulva n=21, cervix n=45, endometrium n=26, fallopian tube n=8 and ovary n=33)

  Dataset EGAD50000000611

• BLUEPRINT release August 2016, ChIP-Seq for band form neutrophil, on genome GRCh38

  ChIP-Seq data for 4 band form neutrophil sample(s). 26 run(s), 23 experiment(s), 23 analysis(s) on human genome GRCh38. Part of BLUEPRINT release August 2016. Analysis documentation available at http://ftp.ebi.ac.uk/pub/databases/blueprint/releases/20160816/homo_sapiens/README_chipseq_analysis_ebi_20160816

  Dataset EGAD00001002454

• Regulatory T cell transcriptomic reprogramming characterizes adverse events by checkpoint inhibitors in solid tumors

  Tregs were sorted as CD4+CD25+CD127- cells from peripheral blood of patients with advanced metastatic melanoma, stage III(B-D)-IV, who were receiving treatment with anti-PD1 (n =26); and patients with kidney, non-small cell lung, liver and bladder cancer who were receiving treatment with anti-PD1. RNA was extracted and polyA libraries were prepared using the Illumina Truseq sample preparation kit v.2. Single-end sequencing was performed on NextSeq500.

  Dataset EGAD00001006415

• Mitochondrial DNA sequencing of human iPSC, parental cells, and iPSC derived cardiomyocytes

  Dataset contains whole mitochondrial DNA sequencing data in fastq format (Illumina MiSeq paired-end) of 62 samples, in total. Those samples include sequencing data of the endothelial cell populations of 10 different donors and of 26 early-passage iPSC clones derived thereof. Moreover, the dataset contains the data of 7 of those iPSC clones sequenced additionally in passage 30 and 50, each. Lastly, 4 iPSC clones were sequenced during directed cardiomyocyte differentiation, each at day 0, 5, and 15 of differentiation.

  Dataset EGAD00001008021

• Synthetic - FEGA Sweden Heilsa synthetic dataset December 2023

  Synthetic - This submission contains a subset of a synthetic dataset derived from the project Heilsa Tryggvedottir - a Nordic collaboration on sharing sensitive human data. Heilsa Tryggvedottir is funded by the Nordic e-Infrastructure Collaboration (NeIC), the ELIXIR nodes of Finland, Norway, and Sweden, Computerome in Denmark, and the Estonian Scientific Computing Infrastructure (ETAIS). In the synthetic data creation process, it was attempted to strike a fine balance between the usability of the datasets (e.g. technical FEGA development, testing, user training, and basic bioinformatics) and compliance with GDPR. File names and file content (e.g. headers in fastq) are anonymized. Moreover, the X, Y, and mitochondrial sequences have been discarded from the original data since these data can be used for maternal, paternal, or ethnic origin tracing. The dataset does not follow natural haplotype distribution (inherent to imputation panels). The only inputs derived from real sequence data are variant distribution density per chromosome and learning sequencing error models. The synthetic dataset consists of two fastq files, a cram file, a vcf file, and two index files.

  Dataset EGAD50000000119