Hi @apunjani, is reference-based motion correction still in the works? We still find polishing gives benefits in a lot of cases beyond what patch motion and reference free local motion correction can do.
E.g. take a look at EMPIAR-10737 (EMPIAR-10737 Cryo-EM structures of E. coli cytochrome bo3 in MSP Nanodiscs) - in this case three rounds of polishing & CTF refinement took resolution from 2.7 to ultimately 2.2Å.
One thing that would improve this even more would be the capacity to perform multireference motion correction, as well as explicit fitting of dose as a parameter (to account for the fact that beam intensity may not be constant during collection, and may differ overall from the nominal value).
Increasingly we are dealing with heterogeneous samples (native cell or membrane extracts) with multiple components resolved to high resolution. In this case it would be useful to perform local motion correction with references matched to each component, to take advantage of the fact that while each component may be sparse individually, together they are crowded, so one can use the assumption that the motion of nearby particles are correlated in order to better restrain fitting of particle trajectories.
Cheers
Oli