Before revision:  Take a recent event for example, after the outbreak of COVID-19 in January, the first structure of 2019-nCoV Spike trimer was published in Marchusing cryo-EM, which has provided crucial medical insight for developing vaccines. The enabler behind this efficiency is the GPU-accelerated computation which shortens the whole analysis process to 12 days. However, the data characteristics include strong noise, huge dimension, large sample size and high heterogeneity with unknown orientations have made analysis very challenging. Though, the popular GPU-accelerated Bayesian approach has been shown to be successful in 3D refinement. It is noted that the traditional method based on multireference alignment may better differentiate subtle structure differences under low signal to noise ratio (SNR).
After revision:  Take a recent event for example, after the outbreak of COVID-19 spike protein in March, shortly after its breakout in late January 2020. This rapidity is critical for vaccine development in response to emerging pandemic. This explains why a 2D classification approach based on multi-reference alignment (MRA) is not as popular as the Bayesian-based approach despite that the former has advantage in differentiating subtle structural variations under low signal-to-noise ratio (SNR).