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
Department of Medical BioSciences, Radboud University Medical Center, Nijmegen, Netherlands.
Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands.
Front Genet. 2024 Sep 19;15:1451024. doi: 10.3389/fgene.2024.1451024. eCollection 2024.
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 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.
人类神经视网膜是一种复杂的组织，具有丰富的可变剪接，超过10%与遗传性视网膜疾病（IRD）相关的基因变异会改变剪接。传统的短读长RNA测序方法已被用于了解视网膜特异性剪接，但在详细描述转录本异构体方面存在局限性。为了解决这个问题，我们生成了一个蛋白质基因组图谱，该图谱将PacBio长读长RNA测序数据与三个健康人类神经视网膜样本的质谱和全基因组测序数据相结合。我们鉴定出近60,000种转录本异构体，其中约三分之一是新发现的。此外，十种新肽证实了新的转录本异构体。例如，我们鉴定出一种具有已知外显子新组合的新异构体，并有肽证据支持。我们的研究强调了深入的组织特异性转录组分析在增强我们对组织特异性可变剪接理解方面的潜力。蛋白质基因组图谱的基础数据可通过EGA获得，标识符为EGAD50000000101，通过ProteomeXchange获得，标识符为PXD045187，并可通过UCSC基因组浏览器访问。
