How to run simple requests on a 100 GB SQLite file in Python?

I have a large SQLite file (100 GB) that I would like to explore a bit. Basically I just want to perform simple computations like pandas.groupby.

Unfortunately any computation is taking ages, even on my powerful machines which have 10 cores, 128 GBs of RAM, etc.

What should I do? What would be the most appropriate way to explore this dataset in Python?