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Nearly all volcano plot I've seen tend to be roughly symmetric around the y-axis, with a fairly equal number of up- and down-regulated genes. What are the potential reasons for a volcano plot that is heavily unbalanced (i.e., many more negative fold change genes than positive)?

In my analysis, I have identified two populations of patients within a disease cohort, representing the "interferon high" and "interferon low" sub-populations. I then calculate differential expression between these groups, and visualize the results with a volcano plot (log(p-value) of differential expression vs. log(fold change)). The volcano plot is quite asymmetric, with a maximum log2 fold change of 1 on the positive end, and a minimum log2 fold change of -3 on the negative end, with many more genes significantly down-regulated in the IFN-low population.

Is it reasonable to suppose that there are lots of genes up-regulated in IFN-high, with no down-regulated genes defining this population, or is there something else going on?

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I have no experience on mammalian expression analysis but I have seen these asymmetric plots quite a few times when cells were highly stressed. During one treatment they shut down protein biosynthesis and photosynthesis so downregulated genes vastly outnumbered the few genes which were involved in the adaptation response. I don't know if something similar could be happening in your samples?

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