RNAseq deconvolution to immune cells

Question

[zizigolu]

Hi

I have bulk RNAseq of two groups of patients

How I know differentially expressed genes are related to which immune cell types?

I have heard about deconvolution idea but I'm not sure if this is applicable to my case

Can somebody help me to get intuition?

Answer 1

[Kevin Blighe]

With just bulk RNA-seq, I would prefer to use either GSVA or GSEA (Broad Institute's JAVA implementation), and that would be using the entire unfiltered dataset. Then, we are referring to gene and pathway 'signatures', as opposed to cell-types. I do not recall any great algorithm or program that was released that can deconvolute bulk RNA-seq. We built one as part of this following publication, and it utilised the FANTOM5 dataset from Japan (i.e., we first built our cell-type signatures using the FANTOM5 data, and then applied these to our bulk RNA-seq data): Molecular Portraits of Early Rheumatoid Arthritis Identify Clinical and Treatment Response Phenotypes.

I have also since developed some other methods for doing similar 'deconvolutions' of one signature to a new datasets, but never published these, due to the fact that the work is protected by non-discolure agreements, etc.

You could also use enrichR using just the differentially expressed genes. This can quickly generate a lot of enrichment results through which you can sift.

Two relatively recent programs that can deconvolute bulk RNA-seq data, however, utilise scRNA-seq data in order to do this. You should take a look at these to see if they are suitable or not:

• BSEQ-sc: Deconvolution of Bulk Sequencing Experiments using Single Cell Data
• MuSiC: Multi-subject Single-cell Deconvolution

BSEQ-sc is interesting, as one of the developers is Renaud Gaujoux, who famously developed one of the very first deconvolution tools based on the Abbas cDNA microarray data, known as 'CellMix'.

Kevin.