Biology subjects

Wessels, H. J. C. T.

Publications and source records attributed to Wessels, H. J. C. T..

2 recordsLinked to original sources

bioRxiv2024

A proteogenomic atlas of the human neural retina

The human neural retina is a complex tissue with abundant alternative splicing and more than 10% of genetic variants linked to inherited retinal diseases (IRDs) alter splicing. Traditional short-read RNA-sequencing methods have been used for understanding retina-specific splicing but have limitations in detailing transcript isoforms. To address this, we generated a proteogenomic atlas that combines PacBio long-read RNA-sequencing data with mass spectrometry and whole genome sequencing data of three healthy human neural retina samples. We identified nearly 60,000 transcript isoforms, of which approximately one-third are novel. Additionally, ten novel peptides confirmed novel transcript isoforms. For instance, we identified a novel IMPDH1 isoform with a novel combination of known exons that is supported by peptide evidence. Our research underscores the potential of in-depth tissue-specific transcriptomic analysis to enhance our grasp of tissue-specific alternative splicing. The data underlying the proteogenomic atlas are available via EGA with identifier EGAD50000000101, via ProteomeXchange with identifier PXD045187, and accessible through the UCSC genome browser. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/595273v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1e0810org.highwire.dtl.DTLVardef@1a382b6org.highwire.dtl.DTLVardef@1da7d9eorg.highwire.dtl.DTLVardef@16d29a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2023

The GlycoPaSER prototype as a real-time N-glycopeptide identification tool based on the PaSER parallel computing platform

Real-time database searching allows for simpler and automated proteomics workflows as it eliminates technical bottlenecks in high throughput experiments. Most importantly, it enables results dependent acquisition (RDA) where search results can be used to guide data acquisition during acquisition. This is especially beneficial for glycoproteomics since the wide range of physicochemical properties of glycopeptides lead to a wide range of optimal acquisition parameters. We established here the GlycoPaSER prototype by extending the Parallel Search Engine in Real-time (PaSER) functionality for real-time glycopeptide identification from fragmentation spectra. Glycopeptide fragmentation spectra were decomposed into peptide- and glycan-moiety spectra using common N-glycan fragments. Each moiety was subsequently identified by a specialized algorithm running in real-time. GlycoPaSER can keep up with the rate of data acquisition for real-time analysis with similar performance to other glycoproteomics software and produces results that are in line with literature reference data. The GlycoPaSER prototype presented here provides the first proof-of-concept for real-time glycopeptide identification that unlocks future development of RDA technology to transcend data acquisition.

bioinformatics↗