Determining the 3D structures of biological molecules is a key problem for both biology and medicine. Electron Cryomicroscopy (Cryo-EM) is a promising technique for structure estimation which relies heavily on computational methods to reconstruct 3D structures from 2D images. This paper introduces the challenging Cryo-EM density estimation problem as a novel application for stochastic optimization techniques. Structure discovery is formulated as MAP estimation in a probabilistic latent-variable model, resulting in an optimization problem to which an array of seven stochastic optimization methods are applied. The methods are tested on both real and synthetic data, with some methods recovering reasonable structures in less than one epoch from a random initialization. Complex quasi-Newton methods are found to converge more slowly than simple gradient-based methods, but all stochastic methods are found to converge to similar optima. This method represents a major improvement over existing methods as it is significantly faster and is able to converge from a random initialization.

There is growing interest in representing image data and feature descriptors using compact binary codes for fast near neighbor search. Although binary codes are motivated by their use as direct indices (addresses) into a hash table, codes longer than 32 bits are not being used as such, as it was thought to be ineffective. We introduce a rigorous way to build multiple hash tables on binary code substrings that enables exact k-nearest neighbor search in Hamming space. The approach is storage efficient and straightforward to implement. Theoretical analysis shows that the algorithm exhibits sub-linear run-time behavior for uniformly distributed codes. Empirical results show dramatic speedups over a linear scan baseline for datasets of up to one billion codes of 64, 128, or 256 bits.