Abstract

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.

Harnessing existing scRNA-seq data, a set of new tip endothelial cell markers is described to demonstrate the need for targeted assessment and prioritization of candidate genes.

Details

Title
Prioritization and functional validation of target genes from single-cell transcriptomics studies
Author
Sokol, Liliana 1 ; Cuypers, Anne 1   VIAFID ORCID Logo  ; Truong, Anh-Co K. 1 ; Bouché, Ann 1 ; Brepoels, Katleen 1 ; Souffreau, Joris 1 ; Rohlenova, Katerina 2   VIAFID ORCID Logo  ; Vinckier, Stefan 1 ; Schoonjans, Luc 3 ; Eelen, Guy 1 ; Dewerchin, Mieke 1   VIAFID ORCID Logo  ; de Rooij, Laura P.M.H. 4   VIAFID ORCID Logo  ; Carmeliet, Peter 5   VIAFID ORCID Logo 

 Leuven Cancer Institute (LKI), Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, KU Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) 
 Leuven Cancer Institute (LKI), Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, KU Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); BIOCEV, Institute of Biotechnology of the Czech Academy of Sciences, Vestec, Czech Republic (GRID:grid.448014.d) 
 Leuven Cancer Institute (LKI), Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, KU Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); Aarhus University, Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus C, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
 Leuven Cancer Institute (LKI), Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, KU Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (GRID:grid.418729.1) (ISNI:0000 0004 0392 6802) 
 Leuven Cancer Institute (LKI), Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, KU Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884); Aarhus University, Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus C, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722); Khalifa University of Science and Technology, Center for Biotechnology, Abu Dhabi, United Arab Emirates (GRID:grid.440568.b) (ISNI:0000 0004 1762 9729) 
Pages
648
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2827014783
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.