Lets say I have 4 wild type samples, that are meant to be my control.

And I have 10 other samples, that each have a unique gene deletion. say gene1 to gene 10

Can I see DE genes between my 4 wild type samples, and my single gene1 sample?

hi Kieran,

Yes, you can run comparisons of the 4 vs the individual samples. What happens in practice is that the dispersion is estimated among the samples with biological replication, as the individual samples do not give any sense of dispersion. You don't have to do anything special in running DESeq2, compared to what you would do if there were biological replicates for all groups.

The caveat with such an analysis is that, the variability could be underestimated by only looking at the WT samples, and the estimate of LFC hinges on a single sample. But this is the best you can do without biological replicates of the gene deletion samples.