AUTHOR=Riepe Tabea V. , Stemerdink Merel , Salz Renee , Rey Alfredo Dueñas , de Bruijn Suzanne E. , Boonen Erica , Tomkiewicz Tomasz Z. , Kwint Michael , Gloerich Jolein , Wessels Hans J. C. T. , Delanote Emma , De Baere Elfride , van Nieuwerburgh Filip , De Keulenaer Sarah , Ferrari Barbara , Ferrari Stefano , Coppieters Frauke , Cremers Frans P. M. , van Wyk Erwin , Roosing Susanne , de Vrieze Erik , ‘t Hoen Peter A. C. TITLE=A proteogenomic atlas of the human neural retina JOURNAL=Frontiers in Genetics VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1451024 DOI=10.3389/fgene.2024.1451024 ISSN=1664-8021 ABSTRACT=

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.