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Asymmetric/biased log2FC values for low-expressed genes in DESeq2

Hello everyone,

I apologize if this question seems a bit naive. When we ran DESeq2 for our scRNAseq data (where we first pseudobulked the data by samples), we observed that genes with low expression (those with low baseMean values) exhibited an asymmetry in the log2FC values, as shown in the graph. However, when we used edgeR, we did not observe this asymmetry or bias. Currently, we have not applied any shrinkage methods such as apeglm or ashr, even though we are aware that using shrinkage methods can potentially resolve this issue.

Do you have any ideas or thoughts on why this might be happening? Thanks!

enter image description here

deseq2 deg fold-change

Why is this an issue? It's not significant. Prefiltering (recommended) will likely solve it. FCs of these genes have large standard error, so it's not reliable.

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