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• Immune Dysregulation in Human Subjects with Heterozygous Germline Mutations in

  We identified germline heterozygous mutations in CTLA4 in members of four families with severe immune dysregulation. Human CTLA4 haploinsufficiency caused dysregulation of FoxP3+ regulatory T (Treg) cells and lymphocytic infiltration of target organs, mimicking Ctla4 homozygous mice. Patients also exhibited a B cell phenotype, with progressive loss of B cells and accumulation of autoreactive CD21lo B cells. This study demonstrates a critical quantitative role for CTLA-4 in human immune homeostasis.

  Study phs000797

• NHLBI TOPMed: Pathways to Immunologically Mediated Asthma (PIMA)

  Study designed to further our understanding of the pathogenesis of asthma exacerbations in children. Children enrolled in the study (n=217) were all asthmatic and primarily Hispanic white. The children were followed for 18 months until they experienced an asthma exacerbation or completed the follow-up without an exacerbation. The time to the first asthma exacerbation was considered the outcome. The acute and convalescent immune phenotype of each asthma exacerbation was documented.

  Study phs001727

• LCM-isolated buccal epithelial cell sequencing

  Single buccal epithelial cells were dissected and collected on an adhesive cap with laser capture microdissection (LCM) with approximately 13-60 cells per cap. Each adhesive cap containing 13-60 cells was independently processed with QIAamp DNA micro kit (Qiagen) for DNA extraction. The NEBNext ultra II FS DNA library kit was used to prepare DNA libraries with low starting material. Paired-end whole genome sequencing reads were obtained with the NovaSeq.

  Study EGAS50000000098

• Single-cell RNA sequencing of pediatric Hodgkin Lymphoma to study the inhibition of T cell subtypes

  Here, we applied single-cell RNA-sequencing (scRNA-seq) on isolated HRS cells and the immune cells from the same pediatric classical Hodgkin Lymphoma (cHL) tumors. Specifically, 13 cHL patients and 3 reactive lymph node control samples were included in this cohort. This allowed us to identify genes of cell surface proteins that are consistently overexpressed in HRS cells and can potentially be used as targets for antibody-drug conjugates or CAR T cells. Finally, we identify potential interactions by which HRS cells inhibit T cells, among which the Galectin-1/CD69 and HLA-DRA/LAG3 interactions. However, high levels of inter-patient heterogeneity of the interaction strength were observed. In conclusion, this study identifies new potential therapeutic targets for cHL and highlights the importance of studying heterogeneity when identifying therapy targets.

  Dataset EGAD50000000626

• Whole genome and transcriptome sequencing of cancer of unknown primary tumours

  Whole genome and transcriptome sequencing of cancer of unknown primary tumours was used to determine yield of clinical biomarkers for a molecular guided trial or for resolving cancer type of origin. This study includes profiling of germline DNA and tumour DNA and RNA by whole genome and transcriptome sequencing. All samples are in BAM format aligned with GRCh38 reference genome. This dataset includes: 1. Whole genome sequencing (WGS) of 78 cancer of unknown primary tumour samples and 73 matched germline DNA. 2. Whole transcriptome sequencing (WTS) of 69 cancer of unknown primary tumour samples (matched to WGS cases) 3. Whole genome sequencing of 22 cell-free DNA samples from cancer of unknown primary patients and matched Germaine DNA(8 samples matched to tumour WGS)

  Dataset EGAD50000000656

• Characterisation of Cyr61-enriched myeloid angiogenic cells

  We previously demonstrated the enrichment of an angiogenic precursor cell population from peripheral blood mononuclear cells by CYR61, a protein of the CCN family. In vivo, CYR61 mediates the binding of leukocytes and particular monocyte populations at sites of vascular inflammation. Here, we present an in vitro enrichment system mimicking (patho)physiology and at the same time representing an effective tool for enrichment of the CYR61-binding blood cells and analyzed this cell population in depth.

  Study EGAS50000000533

• Transcriptome Sequencing PPGL (2)

  RNA-Seq data (n=81) library preparation was performed as previously reported by Calsina et al 2023 using QuantSeq 3' mRNA-Seq Library Prep Kit FWD for Illumina (Lexogen, 015). The prepared libraries were subsequently sequenced on NovaSeq™ system (Illumina). To combine the new CNIO samples (n=81) with the CNIO+TCGA dataset generated in Calsina et al., 2023, RNA data were processed using ComBat-seq as described in that same article.

  Study EGAS50000000013

• Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways

  Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.

  Study EGAS50000000367

• Reconstitution of Human Brain Cell Diversity in Organoids via Four Protocols [scRNAseq]

  Single-cell RNA-sequencing of brain organoids at day 120 grown in four distinct growth protocols designed to generate dorsal (D) and ventral (V) forebrain, midbrain (M) and striatum (S) tissue using eight different pluripotent stem cell lines. Per per cell line-protocol combination two organoids (biological replicates) were grown. For cell line 176 the experiment was conducted in two independent biological replicates (repititions E1 and E2).

  Study EGAS50000000662

• Targeting Heterochromatin Eliminates Malignant Stem Cells in Chronic Myelomonocytic Leukemia Through Reactivation of Retroelements and Innate Immune pathways

  Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In this study we analyze heterochromatin and transcriptomic changes occurring at genes and TEs in HSCs from chronic myelomonocytic leukemia, a severe myeloid malignancy affecting the elderly, compared to age-matched cells, and in the presence or absence of a combination of epidrugs.

  Study EGAS50000000688