Prioritization and functional validation of target genes from single-cell transcriptomics studies
Liliana Sokol1, Anne Cuypers1, Anh-Co K Truong1
1Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB and Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, Belgium.
Communications Biology
|June 17, 2023
Summary
Prioritizing candidate genes from single-cell RNA sequencing (scRNA-seq) studies is crucial for translating research into clinical practice. Functional validation confirmed four of six prioritized tip endothelial cell markers, highlighting a pathway for therapeutic target discovery.
Area of Science:
- Biomedical research
- Molecular biology
- Translational medicine
Background:
- Translating academic findings into clinical practice remains a significant challenge in medicine.
- Single-cell RNA sequencing (scRNA-seq) generates extensive lists of potential functional markers, but functional validation is often lacking.
- Prioritizing candidate genes is essential due to the time and cost associated with validation studies.
Purpose of the Study:
- To develop a method for in silico prioritization of novel or poorly characterized tip endothelial cell (EC) marker genes.
- To identify high-ranking tip EC markers from scRNA-seq data for functional validation.
- To assess the potential of prioritized genes for therapeutic target discovery in angiogenesis.
Main Methods:
- Tailoring the Guidelines On Target Assessment for Innovative Therapeutics (GOFAI) framework for gene prioritization.
- In silico prioritization of tip EC marker genes identified through scRNA-seq.
- Functional validation of selected candidate genes in endothelial cells.
Main Results:
- Six high-ranking, previously unreported or poorly described tip EC marker candidates were prioritized.
- Functional validation confirmed that four of the six prioritized candidates indeed function as tip EC genes.
- A novel tip EC function was identified for a gene with limited prior annotation.
Conclusions:
- In silico prioritization of scRNA-seq data, guided by established assessment frameworks, can effectively identify functionally relevant genes.
- Validated tip EC markers derived from scRNA-seq offer promising avenues for therapeutic target identification.
- Not all top-ranked markers from scRNA-seq studies necessarily perform their predicted functions, underscoring the need for rigorous validation.
