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• Combinatorial Indexed 10x Genomics Single-Cell ATAC-seq on Human Cerebral Cortex

  Single-cell chromatin accessibility profiling (scATAC) using droplet fluidics (10x Genomics) is inherently limited in throughput due to the number of available indexed droplets. This study leverages single-cell combinatorial indexing workflows with modified adapter designs to enable indexed tagmentation and superloading of pre-indexed nuclei into the 10x Genomics scATAC workflow, enabling a substantial increase in the number of cell profiles that can be obtained per channel. This workflow, 10x single-cell combinatorial indexed ATAC-seq (txsciATAC), is demonstrated on human brain tissue (middle frontal gyrus), along with mouse brain tissue to enable doublet and crosstalk assessment. This study includes all human data and includes a single preparation taken through nuclei isolation and indexed tagmentation using 96 indexes then split to produce two datasets, one targeting 20k cells and one targeting 70k, each using a single channel of the 10x Chromium controller.

  Study phs003497

• Akershus University Hospital Data Access Committee for Immunoglobulin Heavy-Chain locus in Multiple Sclerosis datasets in FEGA Norway

  This is the Data Access Committee appointed by Akershus University Hospital (AHUS) for datasets from Immunoglobulin Heavy-Chain locus in Multiple Sclerosis studies.

  Dac EGAC50000000659

• Epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages

  Immune memory is key to effective antimicrobial responses, but the impact of mRNA vaccines on this process is not fully understood. Our research shows that SARS-CoV-2 mRNA vaccines alter the epigenetic profile of human macrophages, specifically enhancing histone acetylation, which is linked to immune training. Significant epigenetic changes, along with increased cytokine release, require two vaccine doses. However, these effects diminish over time but can be restored with a booster dose six months later, maintaining a strong pro-inflammatory response.

  Study EGAS50000000341

• Identifying genetic variants that alter TCR usage in the peripheral repertoire

  The relationship between genetic variation and CD8+ T-cell receptor (TCR) repertoire usage in patients receiving Immune Checkpoint Blockade (ICB) therapy for cancer is unexplored. We have conducted a genome-wide and human leukocyte antigen (HLA)-focused analysis of CD8+ T-cell TCR repertoire to identify genetic determinants of variable gene (V-gene) and CDR3 K-mer usage from samples taken prior to and after ICB (n=250). We identify 11 cis and 10 trans V-gene associations, primarily to the MHC, that meet genome-wide significance. TCR clones containing HLA associated V-genes were less stable across treatment, whilst at the single-cell level, genetically associated clones demonstrate subset enrichment and increased tumor reactivity expression profiles. Notably, patients with HLA-matched TCR clones demonstrate improved overall survival. Our work indicates a complex relationship between genotype and TCR repertoire in the context of ICB treatment, with novel implications for understanding factors relating to therapeutic response and patient outcomes.

  Study EGAS00001008189

• Analysis of four key cell types (epithelial, fbroblast, myeloid and T cells)

  Alterations of the normal prostate epithelial cell genome trigger the emergence of carcinoma, however cancer-only analyses of genomic aberrations have resulted in little clinical translation. A deep understanding of the tumor microenvironment is likely to inform on key drivers of disease progression and novel therapeutic opportunities. We investigated the role of key cell types along disease progression, profiling the RNA abundance of 52 samples from 13 patients enriched for one of four key cell types, spanning a wide CAPRA-S risk score range. Using a novel differential transcription Bayes method, TABI, we avoided a priori patient stratification, and mapped transcriptional alteration events to specific risk scores. The developmental and cell-type resolution yielded a landscape of concurrent transcriptional alterations from the tumour microenvironment, including key hallmarks. These transcriptional signatures permitted the identification of a “high survival” patient cluster in an independent prostate cancer dataset. Most importantly, together with our integrated transcriptional analysis, differential tissue composition analysis provided evidence for a key role for monocytes and macrophages in prostate cancer progression and disease recurrence.

  Study EGAS00001003579

• Cergentis FFPE-TLC sequencing of colorectal carcinoma

  In this study, formalin-fixed paraffin-embedded targeted locus capture (FFPE-TLC) sequencing is used as a novel technology for targeted detection of tumor-specific genomic structural variants (SVs) in the primary tumor of 29 colorectal cancer patients with metastatic disease. The tumor region was macrodissected and sequenced for 29 patients, and the "normal" region of the same slide was macrodissected and sequenced for 8 of these patients. SVs were found in the common fragile site (CFS)-associated genes MACROD2, PRKN, FHIT and WWOX as well as SVs caused by three LINE transposable elements. Tumor-specificity of selected SVs was independently verified by droplet digital PCR of tumor tissue DNA and their applicability as plasma circulating tumor DNA biomarkers was demonstrated. This dataset contains the hg19 reference alignment of the FFPE-TLC sequences for all 29 colorectal cancers and 8 adjacent normals.

  Dataset EGAD50000000618

• Acral Melanoma PDXs from the admixed Brazilian Population- Tumour RNA expression data - htseq count files

  Files containing the read counts obtained with obtained with HTSeq for all the genes in Ensembl v103 annotation for GRCh38 human reference genome. This dataset contains the files for all Tumour samples. Acral melanoma (AM) is an aggressive melanoma subtype with limited therapeutic options and poor outcomes. In non-European descent and admixed populations, like in Latin America, it can account for a significant proportion of cutaneous melanoma cases. Here, we performed comprehensive genomic and functional profiling of AM from a uniquely diverse Brazilian cohort. Whole-exome and transcriptome sequencing was performed on both tumours and patient-derived xenograft (PDX) samples. The PDX were obtained from a comprehensive collection of patient-derived xenograft (AM-PDX) models that we established which faithfully retained the histopathological and genomic features of the original tumours.

  Dataset EGAD00001015745

• The_International_1q_type_2_diabetes_consortium

  The aim of this project is to identify rare variants in the 1q region associated with type 2 diabetes. To this end 651 case samples and 651 control samples from six populations have been pooled (pool sizes range from 27-33 individuals), and are being sequenced. The hybridization solution being used captures the exons and UTRs of genes in the 1q region.

  Study EGAS00001000062

• Genetics of Schizophrenia in an Ashkenazi Jewish Case-Control Cohort

  Schizophrenia is characterized by high heritability (~80%), yet the identification of susceptibility genes has proven extremely challenging. The Ashkenazi Jewish population, derived from a limited number of founders, may be enriched for a subset of susceptibility alleles, which may also have higher odds ratios than those detected by previous studies. GWAS was conducted in a large Ashkenazi case-control cohort, derived from the Hebrew University Genetic Resource, using the Illumina HumanOmni1-Quad BeadChip.

  Study phs000448

• Hereditary_Cerebellar_Ataxias___Whole_Genome_Sequencing___2021

  Looking to identify mutations in order to validate that lines we have classified as from Ataxia patients contain the disease relevant mutations. This will allow us to publish on the existance of these lines which are now commercially avalable. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001006234