A Representation Theory Perspective on Simultaneous Alignment and Classification

Single particle cryo-electron microscopy (EM) is a method for determining the 3-D structure of macromolecules from many noisy 2-D projection images of individual macromolecules whose orientations and positions are random and unknown. The problem of orientation assignment for the images motivated work on general multireference alignment. The recently introduced non-unique games framework provides a representation theoretic approach to alignment over compact groups, and offers a convex relaxation which is formulated as semidefinite programs with certificates of global optimality under certain circumstances. One of the great opportunities in cryo-EM is studying heterogeneous samples, containing two or more distinct classes or conformations of molecules. Taking advantage of this opportunity presents an algorithmic challenge: determining both the class and orientation of each particle. We generalize multireference alignment to a problem of alignment and classification, and we propose to extend non-unique games to the problem of simultaneous alignment and classification with the goal of simultaneously classifying cryo-EM images and aligning them within their respective classes.