Ontology highlight
ABSTRACT:
PROVIDER: PRJEB22275 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Full-length HLA class II sequences
| PRJEB42469 | ENA
Project description:Stop-loss mutations cause over twenty different diseases. The effects of stop-loss mutations can have multiple consequences that are, however, hard to predict. Stop-loss in ITM2B/BRI2 results in C-terminal extension of the encoded protein and, upon furin cleavage, in the production of two 34 amino acid long peptides, ADan and ABri, that accumulate as amyloids in the brains of patients affected by familial Danish and British Dementia. To systematically explore the consequences of Bri2 C-terminal extension, here, we measure amyloid formation for 676 ADan substitutions and identify the region that forms the putative amyloid core of ADan fibrils, located between positions 20 and 26, where stop-loss occurs. Moreover, we measure amyloid formation for ~18,000 random C-terminal extensions of Bri2 and find that ~32% of these sequences can nucleate amyloids. We find that the amino acid composition of these nucleating sequences varies with peptide length and that short extensions of 2 specific amino acids (Aliphatics, Aromatics and Cysteines) are sufficient to generate novel amyloid cores. Overall, our results show that the C-terminus of Bri2 contains an incomplete amyloid motif that can turn amyloidogenic upon extension. C-terminal extension with de novo formation of amyloid motifs may thus be a widespread pathogenic mechanism resulting from stop-loss, highlighting the importance of determining the impact of these mutations for other sequences across the genome.
2024-08-02 | GSE270792 | GEO
Project description:Spliced peptides are short protein fragments spliced together in the proteasome by peptide bond formation. True estimation of the contribution of proteasome-spliced peptides (PSPs) to the global Human Leukocyte Antigen (HLA) ligandome is critical. A recent study suggested that PSPs contribute up to 30% of the HLA ligandome. We performed a thorough reanalysis of the reported results using multiple computational tools and various validation steps and concluded that only a fraction of the proposed PSPs passes the quality filters. To better estimate the actual number of PSPs, we present an alternative workflow. We performed de-novo sequencing of the HLA-peptide spectra and discarded all de-novo sequences found in the UniProt database. We checked whether the remaining de-novo sequences could match spliced peptides from human proteins. The spliced sequences were appended to the UniProt fasta file, which was searched by two search tools at a FDR of 1%. We find that 2-6% of the HLA ligandome could be explained as spliced protein fragments. The majority of these potential PSPs have good peptide-spectrum match properties and are predicted to bind the respective HLA molecules. However, it remains to be shown how many of these potential PSPs actually originate from proteasomal splicing events.
2018-09-03 | PXD010793 | Pride
Project description:The identification of promoter and upstream regulatory sequences is an key step towards understanding gene regulation; to this aim, primer extension techniques, which can be performed transcriptome-wide, are the first step, as they allow the location of experimental transcription start sites and other features (such as
2019-07-31 | E-MTAB-6124 | biostudies-arrayexpress
Project description:Our extended analysis of the HLA-presented antigen landscape in cervical cancer cells using an integrative proteogenomics approach identifies, next to tumour-associated antigens and tumour-specific neoantigens, presentation of viral canonical, and alternative reading frame (ARF)-derived HLA-presented sequences, including peptides derived from HPV-E1.
2023-03-11 | PXD028738 | Pride
Project description:Data dependent mass spectrometry (MS) is routinely used to identify HLA-bound peptides but it can have limitations in sensitivity and reproducibility. We introduce Pepyrus, a method that uses E. coli to generate large-scale user-defined peptide libraries that can be utilized to improve the confidence in identification of HLA-bound peptides, including lowly abundant neoantigens. Using a Pepyrus peptide library paired with an HLA-specific data independent acquisition (DIA) MS strategy, we recovered >75% of the expected sequences per single injection for libraries of >10,000 peptides. Pepyrus peptide libraries also enabled the identification of 0.1 fmol spiked-in peptides in a complex background. Application of Pepyrus to create personalized peptide libraries facilitated the identification of clinically relevant HLA antigens from melanoma and renal cell carcinoma patient derived cell lines, several of which were previously undetected. Pepyrus customization enables rapid creation of patient- or disease-specific peptide libraries facilitating the confident identification of rare HLA peptides from immunopeptidomics data and the generation of large training datasets to improve spectrum, retention time, and IM prediction tools.
2025-11-20 | GSE309497 | GEO
Project description:HLA-I molecules bind short peptides and present them to CD8+ T cells for TCR recognition. The length of HLA-I ligands typically ranges from 8 to 12 amino acids, but high variability is observed between different alleles. Here we used recent HLA peptidomics data to analyze in an unbiased way peptide length distributions over 85 different HLA-I alleles. Our results revealed clear clustering of HLA-I alleles with distinct peptide length distributions, which enabled us to unravel some of the molecular basis of peptide length distributions and predict peptide length distributions based on HLA-I sequences only. We further took advantage of our collection of curated HLA peptidomics studies to investigate multiple specificity in HLA-I molecules and validated these observations with binding assays. Explicitly modeling peptide length distributions and multiple specificity significantly improved predictions of naturally presented HLA-I ligands, as demonstrated in an independent benchmarking based on ten newly generated HLA peptidomics datasets from meningioma samples.
2019-07-31 | PXD009925 | Pride