Is scRNA-seq always superior to bulk RNA-seq?

Single-cell RNA sequencing (scRNA-seq) has transformed biological research by providing remarkable resolution for studying gene expression at the level of individual cells. This detailed view is invaluable for studying cellular diversity, identifying rare cell types, and understanding complex tissues like the brain or tumor microenvironments.

However, does this mean scRNA-seq is always a better choice than bulk RNAseq? Not necessarily.

Depth vs. breadth

While scRNA-seq allows for sequencing a very high number of individual cells, it comes at the cost of reduced sequencing depth. In contrast, bulk RNA-seq enables deeper sequencing, providing a more comprehensive view of gene expression across the entire sample. This makes bulk RNA-seq more suitable for detecting low-abundance transcripts or capturing subtle expression changes across conditions.

Biological insights

When the main focus of research is understanding broad gene expression patterns, such as comparing gene expression between tissues or across conditions, bulk RNA-seq can provide clear and actionable insights without the need for the added complexity of single-cell analysis. For example, in drug development, bulk RNA-seq can be instrumental in discovering genes with different expression profiles between treated and untreated groups, making it easier to understand the effects of a treatment.

Cost and complexity

If your research question doesn’t require razor-sharp single-cell resolution, scRNA-seq can be significantly more expensive and technically challenging than bulk RNA-seq. For large-scale studies or projects with limited budgets, bulk RNA-seq offers a more feasible and cost-effective solution.

In essence, the best approach depends on your specific research goals. It is not about which technology is superior, but rather about choosing the right tool for the right question.

Written by: Vilija Lomeikaitė, PhD, Miglė Gabrielaitė, PhD, Ingrida Olendraitė, PhD
Cover image credits: Olena / Adobe Stock