I've got a question related to some pretty dramatic differences I'm seeing in a DESeq2 analysis depending on whether or not I use lfcshrink on the results.
Here is what the "standard" results of my analysis look like:
res <- results(ddsTxi) print(summary(res)) out of 28221 with nonzero total read count adjusted p-value < 0.1 LFC > 0 (up) : 3, 0.011% LFC < 0 (down) : 2, 0.0071% outliers  : 206, 0.73% low counts  : 0, 0% (mean count < 0)
In this case, there are virtually no DEGs.
However, if I use lfcshrink:
resLFCshrink <- lfcShrink(ddsTxi, coef=2, type="apeglm") print(summary(resLFCshrink)) out of 28221 with nonzero total read count adjusted p-value < 0.1 LFC > 0 (up) : 2987, 11% LFC < 0 (down) : 976, 3.5% outliers  : 206, 0.73% low counts  : 3273, 12% (mean count < 1)
there are many DEGs!
I've never seen such a dramatic difference between the "standard" results and the lfcshrink results. The latter results are more in keeping with what I was expecting, however the difference is so big I'm worried that I shouldn't be trusting these results at all.
Assuming that this is an abnormal situation, does anyone have suggestions for steps I might take to investigate what is going on here?