You are asking all the right questions! Yes, you can use denoise-single on paired-end reads if R2 has too low quality.
Which 16S region did you sequence? I ask because depending on the length of this region, you may have enough coverage where you can still use both reads with some appropriately short trimming settings for R2.
Hello, thank you for your response. I sequenced the V3-V4 region. From what I understand, this region is quite long, so you really need both reads in good shape to get enough overlap for merging. In my case, R2 drops in quality so fast that, even trimming it short, the overlap becomes too small to merge reliably. That’s why I’m considering using denoise-single on R1 only…