Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

4f-SAMMY-seq (Sequential Analysis of MacroMolecules Accessibility) and total RNA-seq data from prostate biopsies of 25 chemo-naïve patients (7 healthy biopsies and 18 tumor biopsies)

ABSTRACT: We used a groundbreaking epigenomic profiling technique developed in our laboratory, the 4f-SAMMY-seq, along with RNA-seq on 7 healthy biopsies and 18 prostate tumor biopsies. Our study represents the first direct examination of chromatin organization in patient-derived prostate biopsies. Leveraging differences in chromatin architecture, we identified a novel Prostate Cancer transcriptional signature associated with a favorable prognosis.

INSTRUMENT(S): Maxwell® RSC 48 Instrument (Promega, AS8500), NextSeq 550, Illumina NovaSeq 6000, Transrectal ultrasound-guided systematic sampling of prostate tissue (TRUS biopsy)

ORGANISM(S): Homo sapiens

SUBMITTER: Chiara Lanzuolo

PROVIDER: E-MTAB-14226 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:the Enhanced Epidermal Antigen Specific Immunotherapy Trial -1 (EEASI) study was a two-centre, open-label, uncontrolled, single-group first-in-human Phase 1A safety study of C19-A3 GNP peptide in individuals with T1D (https://clinicaltrials.gov/ct2/show/NCT02837094). The investigational medicinal product (IMP) was C19-A3 GNP (Midacore™), which comprises Midacore™ GNPs (Midatech Pharma Plc, Cardiff, UK)(1, 20) of a size of less than 5 nm, covalently coupled to an 18-amino acid human peptide, the sequence of which is identical to the residues from position 19 in the C-peptide of proinsulin through to position 3 on the A-chain of the same molecule (GSLQPLALEGSLQKRGIV). The peptide is synthesised with a linker to facilitate binding to the GNPs: 3-mercaptopropionyl-SLQPLALEGSLQKRGIV 2 acetate salt (disulfide bond). The chemical composition of the IMP contained a ratio of 4 C19-A3 peptides: 11 glucose C2: 29 glutathione ligands as determined by 1H-NMR (proton nuclear magnetic resonance). A typical batch contained: [C19-A3 peptide] = 1.33 mg/ml; [gold] = 5.5 mg/ml; [glucose linker] = 0.6 mg/ml; [glutathione linker] = 1.79 mg/ml. As the drug substance was diluted 1:7 to 1:10, depending on the content of C19-A3 peptide per particle, and as 50 μl of the diluted solution was administered to the study participants, this corresponded to C19-A3 peptide: 10 μg; gold: 39 μg; glucose linker: 4.3 μg; glutathione: 12.7 μg. Participants diagnosed with T1D and confirmed to possess the HLA-DRB1∗0401 genotype, were given three doses of C19-A3 GNP at 4-weekly intervals (weeks 0, 4, and 8) in the deltoid region of alternate arms (2 doses in one arm and 1 dose in the other arm) via CE-marked 600 μm length MicronJet600™ hollow microneedles (NanoPass Technologies Ltd. Israel) attached to a standard Luer-lock syringe. The single-dose given in 50 μl volume was equivalent to 10 μg of C19-A3 peptide. Punch skin biopsies of the local area were performed under aseptic conditions and under local anaesthetic (Lidocaine Hydrochloride Injection BP 2%, w/v), using a 6-mm sterile disposable biopsy punch. Following the biopsy, samples were divided with half immediately placed in 10% formalin and transported to the laboratory and the other half placed in RNA laterTM (Fisher Scientific, Loughborough, UK) for bulk RNA sequencing. Control skin samples were obtained from female patients aged 19–82 years, following mastectomy or breast reduction after informed consent. Skin without obvious pathological findings, which was surplus to diagnostic histopathology requirements, was used in the experiments. Control punch biopsy samples were treated in the same manner as described above. After cutting skin samples into small pieces, samples were homogenised and lysed by using Tissue Raptor II and QIAzol® Lysis protocol (QIAzol® Handbook 2021, QIAgen, Crawley, UK). The quality of RNA was routinely assessed by determining the A260:A280 ratio using NanoDrop2000 (Thermo Scientific, UK). RNA libraries were created using TruSeq stranded Total RNA with ribozero GOLD (illumina, UK) and sequenced on an illumina HiSeq 2500 platform with 2 x 75 bp reads

Dataset Information

4f-SAMMY-seq (Sequential Analysis of MacroMolecules Accessibility) and total RNA-seq data from prostate biopsies of 25 chemo-naïve patients (7 healthy biopsies and 18 tumor biopsies)

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