How to analysis the DEGs between smartseq2 data and 10x data

[Linxiaobuskiy]

Hi Seurat community!

I've been contemplating this issue for a while. I'm comparing the same cell type across two datasets that used different sequencing technologies: Smart-seq2 for the control condition and 10x for the disease condition. This introduces a significant batch effect due to the technological differences. I assume that a corrected matrix should be used for DEG analysis. However, I noticed in discussions such as issue #5881 that it is often recommended to use the RNA assay for DEGs analysis, which has left me confused. How can I ensure that the DEGs reflect the biological condition (control vs. disease) rather than the sequencing technology differences?