Before revision:  While MSMs can be learned from trajectories whose starting points are not sampled from an equilibrium ensemble, TICA and VAC have as yet not enjoyed this property, and thus previous TICA /VAC estimates have been strongly biased when used with ensembles of short trajectories .
After revision:  While MSMs can be learned from trajectories whose starting points are not sampled from an equilibrium ensemble, TICA and VAC have as yet not enjoyed this property, and thus previous TICA /VAC estimates have been strongly biased and thus not variationally optimal .