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• Non-coding mutations reveal cancer driver cistromes in luminal breast cancer

  A dataset of ER+PR+ breast tumor samples that were analyzed in order to identify mutation enrichment in cis-regulatory elements and cistrome. The repository includes sequencing data from 88 patients. 26/88 were sequenced using ATAC-seq

  Dataset EGAD00001007650

• SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]

  CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through sporadically emerging escape mutations in MHC- I restricted viral epitopes.

  Study EGAS00001005060

• Multi-omics datasets (WES, RNA-seq) of mesothelioma MIST2 study, a phase II CDK4/6 (abemaciclib) clinical trial

  This study comprises 26 mesothelioma patients with whole exome and RNA sequencing, to to assess potential sensitivity to CDK4/6 inhibition in p16ink4A-negative mesothelioma.

  Study EGAS50000001823

• Long-read data (PacBio)

  The goal of this project was to perform long-read RNA sequencing (LR-seq, PacBio) in combination with short-read RNA-seq for systematic characterization of the isoform diversity in primary breast tumor samples. We sequenced the full-length transcriptomes of 26 breast tumors and 4 normal breast samples.

  Dataset EGAD00001006597

• Human Dicer is required for cell-intrinsic immunity to self-dsRNA

  Self-derived double-stranded RNAs (self-dsRNAs) can activate cell-intrinsic innate immune responses and contribute to autoinflammation. We uncover an essential role for human Dicer in innate immune responses to self-dsRNA. Loss of Dicer disrupts RIG-I-like receptor-dependent type I interferon (IFN-I) induction and activation of both the PKR and OAS1-3/RNAse L pathway in conditions where self-dsRNA accumulates, such as cells lacking ADAR1, PNPase, hnRNPC, or MPP8. In contrast, Dicer does not affect the IFN-I response triggered by exogenous dsRNA. Dicer interacts with LGP2, G3BP1, and Staufen1 and loss of these proteins similarly impairs IFN-I induction by self-dsRNAs. Depletion of Dicer and G3BP1 reduces the accumulation of immunostimulatory self-dsRNAs, while depletion of Dicer and Staufen1 prevents MDA5 oligomerization. We conclude that Dicer regulates self-dsRNA availability and sensing, aided by G3BP1 and Staufen1, respectively. Our findings highlight a non-canonical role for Dicer in innate immune activation by self-dsRNA and pinpoint new drug targets in autoinflammatory disorders.

  Study EGAS50000001409

• Tremelimumab +/- durvalumab in combination with paclitaxel as immune induction in metastatic urothelial cancer: clinical and translational results of the ICRA trial

  DESCRIPTION: New therapeutic strategies for therapy-refractory metastatic urothelial carcinoma (mUC) patients are still needed. In the phase I-II ICRA trial, we evaluated whether paclitaxel plus tremelimumab (T; anti-CTLA-4), with or without durvalumab (D; anti-PD-L1), could induce a tumor response in mUC patients who had already received platinum chemotherapy and immune checkpoint inhibition (ICI). After a dose-escalation safety phase, patients were randomized between three arms: A (n=20 after expansion) paclitaxel plus T750mg (cycles 2-8); B (n=12) paclitaxel plus T300mg (cycle 2) plus D1500mg (cycles 2-13); C (n=12) T750mg (cycles 1-7). The objective response rate in arm A was 26% (88% confidence interval (CI) = [14,36%]) versus 17% (88% CI = [3,42%]) in arm B and 8% (88% CI = [0.3,33%]) in arm C. Grade 3-4 treatment-related adverse events occurred in (A) 45%, (B) 75%, and (C) 25% of patients. Murine experiments showed attenuated tumor outgrowth for paclitaxel plus anti-CTLA-4 compared to monotherapy with either agent. Transcriptomic analyses showed upregulation of inflammation signatures in on-treatment tumor tissue biopsies. This study demonstrated encouraging antitumor activity in therapy-refractory mUC treated with paclitaxel plus high-dose anti-CTLA-4 and suggests immune induction may still be possible after failure to anti-PD-(L)1 therapy. PROJECT GOAL: We aimed to explore both potential biomarkers for response to combination ICB, as well as treatment dynamics to gain a better understanding of the effects of ICB on the urothelial cancer tumor microenvironment (TME).

  Study EGAS50000001574

• 1M-scBloodNL

  Here we present the 1M-scBloodNL study, in which we performed single-cell RNA-seq on 120 individuals of the Northern Netherlands population cohort Lifelines. For each individual peripheral blood mononuclear cells (PBMCs) were sequenced in an unstimulated condition, and after 3 and 24 hour in vitro stimulation with C. albicans (CA), M. tuberculosis (MTB) and P. aeruginosa (PA), totalling approximately 1.3 million cells. scRNA-seq was conducted with the 10X Genomics 3'-end v2 (72 libraries) and v3 (33 libraries) technology. In general, each library contains PBMCs from 8 donors and 2 different stimulation-timepoint combinations. Donors were demultiplexed using a combination of SoupOrCell (https://www.nature.com/articles/s41592-020-0820-1) and genotype information to assign the correct donor to a donor-specific cell cluster.

  Dataset EGAD00001007764

• MSI-Exome-DAC Team Microsatellites Instability and Cancer, INSERM Hospital Saint-Antoine, Paris 12, France Carte d'identité des tumeurs, French league against cancer, Paris France

  Dac EGAC00001000665

• endogene.bio

  The Endogene Bio Data Access Committee oversees and manages access to controlled genomic and clinical datasets deposited by the Endogene Bio research team.

  Dac EGAC50000000786

• scMultiome (snRNA + snATAC) data of 26 regionally sampled GBM tissue from 6 patients

  This dataset contains snRNA-seq data of 26 regionally sampled GBM tissue (peritumoral region, tumor edge, and tumor core). Regionally sampled GBM patient tissue was dissociated and nuclei were processed unsorted or by sorting with 7AAD to remove debris and dead cells. Single-nuclei suspension was prepared following the nuclei isolation protocol Single Cell Multiome ATAC + Gene Expression Sequencing protocol using Chromium Nuclei Isolation Kit. Single-nuclei suspension was prepared following the nuclei isolation protocol Single Cell Multiome ATAC + Gene Expression Sequencing protocol using Chromium Nuclei Isolation Kit, nuclei were barcoded and RNA and ATAC libraries were constructed, allowing for simultaneous capture of transcriptome and epigenome from the same cells.

  Dataset EGAD50000001838