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• 59 CLPD-NK cases WGS & WTS data

  For the cohort of 59 samples, we performed TruSeq DNA PCR-Free whole-genome sequencing library preparation according to manufacturer’s instructions (llumina, ILMN, San Diego, CA) on the automated NGS Star liquid handling platform (Hamilton, Bonaduz, Switzerland) followed by 2x150 bp paired-end sequencing on the HiSeqX or NovaSeq6000 (ILMN). An average coverage of >100x was achieved. For whole transcriptome analysis, the TruSeq Total Stranded RNA kit was used, starting with 250 ng of total RNA, to generate RNA libraries following the manufacturer’s recommendations (ILMN). 2x100bp paired-end reads were sequenced on the NovaSeq 6000 with a median of 50 mio. reads per sample (ILMN).

  Dataset EGAD00001008558

• M116 CHIP Amplicon Sequencing

  Genomic DNA was obtained from M116 peripheral blood sample and was used for targeted deep sequencing (TDS) studies. Barcoded libraries were prepared according to the manufacturer’s instructions, using a probe-based panel (KAPA HyperCap, Roche®) targeting frequently mutated regions of 50 myeloid-related genes. Samples were run on a MiSeq (Illumina®) sequencer for paired-end 2x75 bp reads with a mean coverage of 1000X.

  Dataset EGAD50000001287

• A non-canonical lymphoblast in refractory childhood T-cell leukaemia

  Single cell mRNAseq of T-ALL samples including presentation samples for 13 with refractory disease and 8 with responsive disease, and Day 28 samples for 8 patients with refractory disease. Also includes bulk mRNA sequencing on 6 of the patients with responsive disease.

  Dataset EGAD50000001128

• Whole-transcriptome characterization of cell-free RNA (cfRNA) in cancer and non-cancer patients

  Whole-transcriptome characterization of cfRNA in cancer (stage III breast [n=46], lung [n=30]) and non-cancer (n=89) participants from the Circulating Cell-free Genome Atlas (NCT02889978). Dataset includes collapsed BAM files for plasma cfRNA from each patient, as well as collapsed BAM files for RNA from matched tumor tissue (when available).

  Dataset EGAD00001006484

• PDAC organoid genomic heterogeneity

  The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. Among the outstanding questions in pancreatic cancer biology are the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoids, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation.

  Study EGAS00001006782

• We describe a method to culture organoids from adult human kidney tissue and describe applications for the culture system.

  Adult Stem Cell (ASC)-derived organoids are 3D epithelial structures that recapitulate essential aspects of their organ of origin. We have developed conditions for the long-term growth of primary kidney epithelial organoids. Cultures can be established from mouse and human kidney tissue, as well as from urine and can be expanded for at least 20 passages (> 6 months). Chromosome numbers remain normal. Human organoids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. BK virus infection of organoids recapitulates in vivo phenomena. Organoids can be established from Wilms nephroblastoma. Kidney organoids from Cystic Fibrosis (CF) patient’s urine allowed ex vivo assessment of treatment efficacy. Finally, organoids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active transport function. Adult kidney-derived organoids allow studies of hereditary, infectious and malignant kidney disease in a personalized fashion.

  Study EGAS00001002729

• High Resolution Maps of the HeLa 3D Genome Using Hi-C

  We use in situ Hi-C to probe the three-dimensional architecture of genomes, constructing haploid and diploid maps of nine cell types (including HeLa). The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1-kilobase resolution. We find that genomes are partitioned into contact domains (median length, 185kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ~10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs 'facing' one another. The inactive X-chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats. The data for the other (non-HeLa) cell types has been uploaded to GEO.

  Study phs001010

• Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

  In this study, we sequenced multiple stages of the B-lineage in elderly individuals and patients with lymphoplasmacytic lymphoma to study whether mutations are accumulated in normal-cell counterparts prior to lymphoma

  Dataset EGAD00001008196

• Linked-Read Whole Genome Sequencing Profiles Structural Variant Landscape of Gliomas with Barcode-Level Evidence

  Structural variants (SVs) play essential roles in glioma oncogenesis and offer prognostic insights, yet the SV landscape of gliomas has not been completely characterized due to previous technological limitations. To comprehensively profile the SV landscape of gliomas, we performed linked-read whole genome sequencing (LR-WGS) on 31 tumour samples from 20 glioma patients. Using barcode-level evidence, we validated known SVs and identified the presence of extrachromosomal DNA containing the EGFR sequence, which correlates with elevated EGFR expression. Additionally, we uncovered rare SVs affecting genes typically mutated by single nucleotide variants (SNVs), including those in the SWI/SNF chromatin remodeling complex. Our analysis also reveals selective chromosomal vulnerabilities to SVs, highlighting certain chromosomes as hotspots for SV accumulation. Collectively, our results demonstrate the utility of LR-WGS in accurately detecting SVs and thoroughly profiling SV landscapes using barcode-level evidence. The insights gained into the synergistic effects of SNVs and SVs on oncogenes further underscore the importance of integrating SV analysis when examining mutations in gliomas.

  Study EGAS50000000947

• Single-Cell Atlas of Human Liver and Blood Immune Cells Across Fatty Liver Disease Stages

  The goal of the study was to investigate immunological correlates of human fatty liver disease progression. We generated a single-cell RNA-seq (scRNA-seq) atlas of immune cells from liver fine needle aspirates (FNAs) and paired peripheral blood mononuclear cells (PBMCs) from a full-spectrum Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) human cohort, using the 3' 10X Genomics platform. Using computational analyses to assess changes in cellular frequencies and function, we found heightened immunoregulatory programs with profibrotic potential alongside a shift from antigen-specific to natural killer cytotoxic functions in the liver with MASH progression. Available data include raw single-cell transcriptomic data (FASTQ files) for each sample type (PBMC, FNA) per patient alongside clinical and histological measurements of fatty liver disease.

  Study phs004044