Single cell RNAseq differential genome wide expression significance

Question

[kanwarjag]

In single cell RNA seq about 5-10 % genome is covered during sequencing. Now is it reasonable to study such set of differential expressed genes to identify a global regulatory network. The question is what should be best to get an overview of all (most) regulatory mechanisms at a genome level - Single cell or bulk RNAseq? I understand ScRNA seq has more value to identify different cell types in an heterogeneous population. Any thoughts?

Answer 1

[GouthamAtla]

Gene regulatory networks should be definitely studied as a cell-type specific events. So its better to study them at single cell level or from highly purified cell-types with bulk RNA-Seq.

SingleCell RNA-Seq is still sparse to study global gene regulatory networks. At most, you could get cell-type specificity of genes. The regulatory networks inferred from scRNA-Seq data are not robust and may give hints but not conclusive as there is lot of expression variability due to technical and biological reasons.

There is a nice review Co-expression in Single-Cell Analysis: Saving Grace or Original Sin? about co-expression in scRNA data which might be useful for you.

There is a paper Renal compartment–specific genetic variation analyses identify new pathways in chronic kidney disease I read recently where the authors performed bulk RNA in different Kidney compartments and got better insights into GWAS of CKD instead of studying the whole tissue. This definitely supports GRN as cell-type specific events.