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 <i>IMPDH1</i> 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.
Authors
- Erik de Vrieze (ORCID: https://orcid.org/0000-0003-3448-3269)
- Erwin van Wyk
- Suzanne E. de Bruijn (ORCID: https://orcid.org/0000-0003-2912-9265)
- Merel Stemerdink (ORCID: https://orcid.org/0000-0002-9222-740X)
- Tomasz Z. Tomkiewicz (ORCID: https://orcid.org/0000-0002-2572-7690)
- Peter A.C. ’t Hoen (ORCID: https://orcid.org/0000-0003-4450-3112)
- Michael Kwint
- Alfredo Dueñas Rey (ORCID: https://orcid.org/0000-0002-4456-6159)
- Renee Salz (ORCID: https://orcid.org/0000-0003-1035-7866)
- Stefano Ferrari (ORCID: https://orcid.org/0000-0003-3983-3328)
- Hans J. C. T. Wessels (ORCID: https://orcid.org/0000-0001-5957-3127)
- Tabea Riepe (ORCID: https://orcid.org/0000-0002-6509-7013)
- Erica G. M. Boonen (ORCID: https://orcid.org/0000-0003-1509-3150)
- Frauke Coppieters (ORCID: https://orcid.org/0000-0001-7224-0992)
- Susanne Roosing (ORCID: https://orcid.org/0000-0001-9038-0067)
- Elfride De Baere (ORCID: https://orcid.org/0000-0002-5609-6895)
- Frans P.M. Cremers (ORCID: https://orcid.org/0000-0002-4954-5592)
- Jolein Gloerich (ORCID: https://orcid.org/0000-0001-5976-8426)
- Filip Van Nieuwerburgh (ORCID: https://orcid.org/0000-0001-8815-5485)
- Barbara Ferrari (ORCID: https://orcid.org/0000-0002-0415-6681)
- Sarah De Keulenaer
- Emma Delanote
Institutions
- Radboud University Nijmegen (NL)
- Ghent University Hospital (BE)
- Radboud University Medical Center (NL)
- Ghent University (BE)
- Maastricht University (NL)
- Veneto Eye Bank Foundation (IT)
Publication Details
- Journal
- Frontiers in Genetics
- Published
- 2024-09-19
- DOI
- https://doi.org/10.3389/fgene.2024.1451024
- Citations
- 2
- Primary Topic
- Genomics and Phylogenetic Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.47