Merging replicates from Encode project

Question

[Nurken]

Hi,

I am planning to download datasets from ENCODE, but I am confused on when and how should I merge the replicates.

For example, There is a CHIP experiment, it has H3K9me3 samples and input samples. H3K9me3 has two biological (isogenic) replicates. Each biological (isogenic) replicate has two technical replicates. Each technical replicate has four runs. In this case, I will download all 32 SRAs. Merge runs using cat, resulting in 8 SRAs (technical replicate level), do FastQC, and trimming. Merge technical replicates using cat, resulting in 4 SRAs (biological replicate level). Align and do the rest of the pipeline keeping the biological replicates separate.

Is this a correct order for merging runs and technical replicates?