As I said, better

> > organize the upper tier roughly according to the timeline of your process

No idea where $set comes from but $replicate could be such a top tier.

so $data[$set][$replicate]{$1}{$2} should have far less memory swapping problems (AFAIS).

(BTW better reserve uppercase var-names to perl buit-ins)

If this structure doesn't fit into your future plans, you most likely want to use a DB anyway.