Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Secreted HLA Fc-Fusion Profiles Immunopeptidome in Hypoxic PDAC and Cellular Senescence

ABSTRACT: Here, we describe a secreted HLA (sHLA) Fc-fusion construct for simple single HLA allele profiling in hypoxic pancreatic ductal adenocarcinoma (PDAC) and cellular senescence. This method streamlines sample preparation, enables temporal control, and provides allele-restricted target identification. Over 30,000 unique HLA-associated peptides were identified across two different HLA alleles and seven cell lines, with ~9,300 peptides newly discovered. The sHLA Fc-fusion capture technology holds potential to expedite immunopeptidomics and advance therapeutic interest in peptide-HLA complexes.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Lisa Kirkemo

LAB HEAD: Jim Wells

PROVIDER: PXD045796 | Pride | 2024-01-26

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Secreted HLA-Fc fusion profiles immunopeptidome in hypoxic PDAC and cellular senescence.

Rettko Nicholas J NJ Kirkemo Lisa L LL Wells James A JA

PNAS nexus 20231214 12

Human leukocyte antigens (HLA) present peptides largely from intracellular proteins on cell surfaces. As these complexes can serve as biomarkers in disease, proper identification of peptides derived from disease-associated antigens and the corresponding presenting HLA is important for the design and execution of therapeutic strategies. Yet, current mass spectrometry methods for immunopeptidomic profiling require large and complex sample inputs, hindering the study of certain disease phenotypes a ...[more]

PMID: 38099269

Similar Datasets

Digital mapping of immunopeptidomes: SWATH-MS

Project description:We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated by SWATH mass spectrometry (MS) from a range a biological sources. This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.

2015-07-14 | PXD001904 | Pride

Digital mapping of immunopeptidomes

Project description:We present a novel mass spectrometry-based high-throughput workflow and an open-source computational and data resource to reproducibly identify and quantify HLA-associated peptides. Collectively, the resources support the generation of HLA allele-specific peptide assay libraries consisting of consensus fragment ion spectra, and the analysis of quantitative digital maps of HLA peptidomes generated from a range of biological sources by SWATH mass spectrometry (MS). This study represents the first community-based effort to develop a robust platform for the reproducible and quantitative measurement of the entire repertoire of peptides presented by HLA molecules, an essential step towards the design of efficient immunotherapies.

2015-07-14 | PXD001872 | Pride

Project description:Novel HLA allele

| PRJNA544422 | ENA

Enhanced salt stress tolerance of rice plants expressing a vacuolar H+-ATPase subunit c1 (SaVHAc1) gene from the halophyte grass Spartina alterniflora Löisel

Project description:From the microarray experiment, many of the 43,311 probes were significantly different: 4,287 (9.9 %) between genotypes (WT and SaVHAc1-rice), 6,761 (15.6 %) between environments (saline or non-saline conditions), and 705 (1.6 %) responded differently to the environment depending upon the genotype. Although a large number of genes showed upregulation in SaVHAc1-rice relative to WT, eighteen genes that showed more than two-fold increase or decrease in transcription in SaVHAc1-rice were considered significantly up- or down-regulated, respectively. Fourteen genes encoding proteins with either ion transport or metal binding function were significantly upregulated. The four genes that showed significant down-regulation in SaVHAc1-rice did not have any functional annotation (hypothetical or expressed proteins). Interestingly, none of the other subunits of vATPase was observed as being affected by SaVHAc1. Two genotypes (transgenic and wildtype), both exposed to two environments (saline and control) for up to 72 hours. Four biological replicates per genotype/environment combination. One sample per array.

2011-12-27 | E-GEOD-34724 | biostudies-arrayexpress

Unsupervised mining of HLA-I peptidomes reveals unsuspected false positives and new binding motifs

Project description:Modern antigen vaccine designs and studies of human leukocyte antigen (HLA)-mediated immune responses rely heavily on the knowledge of HLA allele-specific binding motifs and computational prediction of antigen-HLA binding affinity. Breakthroughs in HLA peptidomics have considerably expanded the databases of natural HLA antigens and enabled detailed characterizations of antigen-HLA binding specificity. However, cautions must be made when analyzing HLA peptidomics data because identified peptides may be contaminants or may weakly bind to the HLA molecules. Here, a hybrid de novo peptide sequencing approach was applied to large-scale mono-allelic HLA peptidomics datasets to uncover new antigens and refine current knowledge of HLA binding motifs. Up to 12-40% contaminations in the form of tryptic peptides were identified in the peptidomics data of HLA alleles whose binding motifs do not involve an arginine or a lysine at the C-terminus. Thousands of these peptides were reported in a community database as positive antigens and might be erroneously used to train prediction models. Furthermore, unsupervised clustering of identified antigens not only revealed additional binding motifs for several HLA class I alleles but also effectively isolated outliers which were confirmed to be false positives in a binding experiment. Overall, our findings expanded the knowledge of HLA binding specificity and indicated that a more careful HLA peptidomics data interpretation protocol is needed to ensure the high quality of community antigen databases.

2021-09-17 | PXD028088 | Pride

A flexible microfluidic system for single-cell transcriptome profiling elucidates phased transcriptional regulators of cell cycle

Project description:Single cell or single nuclei RNA sequencing of mixed HEK 293 and 3T3 populations using the Nadia droplet sequencing platform. Samples cover different numbers of beads from which cDNA libraries were prepared.

2021-04-10 | E-MTAB-10296 | biostudies-arrayexpress

RNA-Seq of FEX1, FEX2 deleted S. cerevisiae (yeast) treated with sodium fluoride against untreated control

Project description:Fluoride is a highly abundant, naturally occurring toxicant that causes oxidative stress, cell cycle arrest, and apoptosis at high concentrations. Our lab has created a fluoride-sensitized yeast model lacking fluoride exporters, FEX1 and FEX2. These yeast undergo cell cycle arrest and apoptosis at over 1000-fold less fluoride concentration than in wild type, and oxidative stress within four hours. To determine the mechanism by which fluoride triggers oxidative stress, we grew cells in 25 mL YPD media at starting O.D. 0.1 in +/- 50 uM NaF. After four hours, the cells were washed twice with sterile water, and RNA was harvested and treated with DNAse. RNA was then sent to the the Yale Center for Genome Analysis for quality analysis with a Bioanalyzer and subsequent poly-A sequencing.

2021-12-02 | E-MTAB-8061 | biostudies-arrayexpress

A large peptidome dataset improves HLA class I epitope prediction across most of the human population

Project description:Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA class I-associated peptides across a large fraction of the human population, we used mass spectrometry to profile >185,000 peptides eluted from 95 HLA-A, -B, -C and -G mono-allelic cell lines. We identified canonical peptide motifs per HLA allele, unique and shared binding submotifs across alleles and distinct motifs associated with different peptide lengths. By integrating these data with transcript abundance and peptide processing, we developed HLAthena, providing allele-and-length-specific and pan-allele-pan-length prediction models for endogenous peptide presentation. These models predicted endogenous HLA class I-associated ligands with 1.5-fold improvement in positive predictive value compared with existing tools and correctly identified >75% of HLA-bound peptides that were observed experimentally in 11 patient-derived tumor cell lines.

2019-12-16 | GSE131267 | GEO

A novel HLA-C*17 allele

Project description:A novel HLA-C*17 allele

| PRJEB25486 | ENA

A new HLA-DRB1*07 allele, identified in a Chinese individual

Project description:A new HLA-DRB1*07 allele

| PRJEB21367 | ENA