Prioritization and functional validation of target genes from single-cell transcriptomics studies

0574539 - BTÚ 2024 RIV GB eng J - Journal Article
Sokol, L. - Cuypers, A. - Truong, A.-C. K. - Bouche, A. - Brepoels, K. - Souffreau, J. - Rohlenová, Kateřina - Vinckier, S. - Schoonjans, L. - Eelen, G. - Dewerchin, M. - De Rooij, L. P. M. H. - Carmeliet, P.
Prioritization and functional validation of target genes from single-cell transcriptomics studies.
Communications Biology. Roč. 6, č. 1 (2023), č. článku 648. E-ISSN 2399-3642
Institutional support: RVO:86652036
Keywords : ENDOTHELIAL GROWTH-FACTOR * MACULAR DEGENERATION * ANGIOGENESIS
OECD category: Biochemistry and molecular biology
Impact factor: 5.9, year: 2022
Method of publishing: Open access
https://www.nature.com/articles/s42003-023-05006-7

Translation of academic results into clinical practice is a formidable unmet medical need. Single-cell RNA-sequencing (scRNA-seq) studies generate long descriptive ranks of markers with predicted biological function, but without functional validation, it remains challenging to know which markers truly exert the putative function. Given the lengthy/costly nature of validation studies, gene prioritization is required to select candidates. We address these issues by studying tip endothelial cell (EC) marker genes because of their importance for angiogenesis. Here, by tailoring Guidelines On Target Assessment for Innovative Therapeutics, we in silico prioritize previously unreported/poorly described, high-ranking tip EC markers. Notably, functional validation reveals that four of six candidates behave as tip EC genes. We even discover a tip EC function for a gene lacking in-depth functional annotation. Thus, validating prioritized genes from scRNA-seq studies offers opportunities for identifying targets to be considered for possible translation, but not all top-ranked scRNA-seq markers exert the predicted function.
Permanent Link: https://hdl.handle.net/11104/0345412