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• Whole genome sequencing informs treatment decision of end-stage metastatic cutaneous angiosarcoma in a patient with Xeroderma Pigmentosum

  Whole genome sequencing (WGS) detects all mutations in a cancer. “Mutational signatures” are patterns of mutations that report the DNA damage and subsequent DNA repair processes that have occurred in cancers. We present a patient with Xeroderma Pigmentosum that developed metastatic angiosarcoma, unresponsive to all lines of sarcoma therapy. Primary tumour WGS revealed a hypermutated tumour, including clonal ultraviolet light-induced mutational patterns (Signature 7) and subclonal signatures of activating mutations of DNA Polymerase-epsilon (POLE)(Signature 10). These signatures are associated with response to immune-checkpoint blockade. Immunohistochemistry confirmed high PD-L1 expression in metastatic deposits. The patient was commenced on anti-PD-L1 therapy and has responded.

  Dataset EGAD00001004786

• Age-specific nasal epithelial responses to SARS-CoV-2 infection : GEX

  In this study, we investigate differences in the cellular landscape and functionality of ex vivo cultured nasal epithelial cells in response to SARS-CoV-2 infection across different age groups: paediatric (<12y), adult (30-50y), and older adults (>70y). We unravel, that while ciliated cells serve as primary sites for viral replication consistently across all age groups, a distinctive goblet inflammatory subtype emerges in infected paediatric cultures, characterized by heightened expression of interferon-stimulated genes and incomplete viral replication. Conversely, older adult cultures infected with SARS-CoV-2 exhibit a proportional surge in basaloid-like cells, which not only facilitate viral dissemination but also demonstrate associations with altered epithelial repair pathways.

  Dataset EGAD00001015345

• ScRNA-seq of PBMC and whole blood samples reveales a dysregulated myeloid cell compartment in severe COVID-19

  In a dual-center, two-cohort study, we performed single-cell RNA-sequencing of whole blood and peripheral blood mononuclear cells to determine changes in immune cell composition and activation in mild vs. severe COVID-19 over time. This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

  Dataset EGAD00001006550

• Detection of cancer cell transcriptomes

  Single cell transcriptomes, generated using chromium 10X 3' sequencing, for two tumour types (AT/RT, and Ewing's sarcoma). For each individual, tumour and normal whole genome sequencing was also obtained using Illumina short read sequencing to an average depth of 30X. These data were used to validate the accuracy of a method for identifying cancer cell transcriptomes based on the allelic shift produced by copy number changes.

  Dataset EGAD00001009005

• RNAseq of blood, fat and muscle samples from 45,X, 46,XX, 46,XY and 47,XXY

  Samples of blood, muscle and fat were collected from individuals with TS (n = 33) and KS (n = 22) and from male (n = 16) and female (n = 44) controls. The RNA-seq libraries were multiplexed paired-end sequenced on an Illumina Novaseq 6000 (100 bp) and subjected to initial quality control using FastQC (BAbraham Bioinformatics). In addition to trimming of low-quality ends, adaptor removal was conducted using Trim Galore with default settings (BAbraham Bioinformatics).

  Dataset EGAD00001010052

• Multi-region targeted Sequencing data of 10 neuroblastoma cases

  To investigate intratumour heterogeneity and to better understand tumour evolution in neuroblastoma, we have performed a multi-region targeted re-sequencing on a total of 140 samples from 9 primary neuroblastomas (2 low-risk, 1 intermediate-risk and 6 high-risk) and 2 relapsed neuroblastoma.

  Dataset EGAD00001008156

• Pathogenic Neurofibromatosis type 1 (NF1) RNA splicing resolved by targeted RNAseq

  Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. an in-house developed tool (QURNAS) was used to calculate the enrichment score (ERS) for each splicing event. RNA enrichment of NF1 and SPRED1 was done using SPET (NUGEN - NF1 only) and using SureSelect (Agilent - NF1 and SPRED1).

  Dataset EGAD00001007978

• Tumor-derived cell lines as pharmacogenomic models to predict therapeutic vulnerabilities in hepatocellular carcinoma

  Hepatocellular carcinoma (HCC) is a heterogeneous aggressive malignancy with low efficacy of current therapies at advanced stages. We integrated molecular and pharmacological profiling of a large panel of liver cancer cell lines (LCCL) to assess their clinical relevance as HCC preclinical models and identify new effective therapies and biomarkers of response. Here, we performed multi-omic analysis including whole-exome, RNA and microRNA sequencing in a series 34 LCCL. Molecular profiles of LCCL and primary HCC were compared and we searched for molecular features associated with drug response. Our panel of LCCL faithfully recapitulated the most aggressive molecular “proliferation class” of HCC.

  Dataset EGAD00001004938

• Target-capture sequencing of FFPE tumor samples from patients diagnosed with NKTL

  211 NKTL FFPE specimens were screened for somatic mutations using deep targeted capture sequencing. FFPE rolls or slides were extracted using QIAamp DNA FFPE Tissue kit (QIAGEN). The FFPE genomic DNA was treated with NEBNext FFPE DNA Repair Mix and assessed by Quant-it PicoGreen dsDNA Assay Kit (Invitrogen). The library was generated from 10-200 ng DNA with SureSelectXT Low Input Target Enrichment System for Illumina Paired-End Sequencing Library (Agilent Technologies) according to manufacturer’s instructions. RNA based probe was designed with SureDesign (Agilent Technologies) to target-capture 140 genes. Next, the captured libraries were pooled in equimolar concentration and sequenced on Illumina Novaseq 6000 platform with SP or S1 chip.

  Dataset EGAD00001005303

• Identification of differentially expressed protein-coding genes in HCC and adjacent non-cancerous tissues

  Twenty samples were collected in pairs, i.e., HCC tissue and adjacent non-cancerous tissue. The collected tissue samples were stored in liquid nitrogen. First, 50 mg of tissue was lysed in TRIzol (Invitrogen) to extract RNA following the manufacturer’s instructions. Next, ribosomal RNA was depleted using a RiboZero Gold kit (Epicentre Bio-technologies). RNA integrity was assessed with an Agilent Bioanalyzer 2100. An RNA-Seq library was generated with the rRNA-depleted samples using an Illumina standard RNA Sample Prep kit according to the manufacturer’s instructions. The library was subsequently sequenced on an Illumina HiSeq2500 as 125-bp paired-ends with approximately 300-bp size selection.

  Dataset EGAD00001003397