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

Autor: Sokol L; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Cuypers A; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Truong AK; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Bouché A; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Brepoels K; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Souffreau J; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Rohlenova K; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium.; Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Prague-West, Czech Republic., Vinckier S; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Schoonjans L; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium.; Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark., Eelen G; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., Dewerchin M; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium., de Rooij LPMH; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium. lderooij@cemm.at.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. lderooij@cemm.at., Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium. peter.carmeliet@kuleuven.be.; Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark. peter.carmeliet@kuleuven.be.; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates. peter.carmeliet@kuleuven.be.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Jun 17; Vol. 6 (1), pp. 648. Date of Electronic Publication: 2023 Jun 17.
DOI: 10.1038/s42003-023-05006-7
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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