SOLVAR: Fast covariance-based heterogeneity analysis with pose refinement for cryo-EM

Cryo-electron microscopy (cryo-EM) has emerged as a powerful technique for resolving the three-dimensional structures of macromolecules. A key challenge in cryo-EM is characterizing continuous heterogeneity, where molecules adopt a continuum of conformational states. Covariance-based methods offer a principled approach to modeling structural variability. However, estimating the covariance matrix efficiently remains a challenging computational task. In this paper, we present SOLVAR (Stochastic Optimization for Low-rank Variability Analysis), which leverages a low-rank assumption on the covariance matrix to provide a tractable estimator for its principal components, despite the apparently prohibitive large size of the covariance matrix. Under this low-rank assumption, our estimator can be formulated as an optimization problem that can be solved quickly and accurately. Moreover, our framework enables refinement of the poses of the input particle images, a capability absent from most heterogeneity-analysis methods, and all covariance-based methods. Numerical experiments on both synthetic and experimental datasets demonstrate that the algorithm accurately captures dominant components of variability while maintaining computational efficiency. SOLVAR achieves state-of-the-art performance across multiple datasets in a recent heterogeneity benchmark. The code of the algorithm is freely available at https://github.com/RoeyYadgar/SOLVAR.

Adversarial Bandit over Bandits: Hierarchical Bandits for Online Configuration Management

Motivated by dynamic parameter optimization in finite, but large action (configurations) spaces, this work studies the nonstochastic multi-armed bandit (MAB) problem in metric action spaces with oblivious Lipschitz adversaries. We propose ABoB, a hierarchical Adversarial Bandit over Bandits algorithm that can use state-of-the-art existing "flat" algorithms, but additionally clusters similar configurations to exploit local structures and adapt to changing environments. We prove that in the worst-case scenario, such clustering approach cannot hurt too much and ABoB guarantees a standard worst-case regret bound of $O\left(k^{\frac{1}{2}}T^{\frac{1}{2}}\right)$, where $T$ is the number of rounds and $k$ is the number of arms, matching the traditional flat approach. However, under favorable conditions related to the algorithm properties, clusters properties, and certain Lipschitz conditions, the regret bound can be improved to $O\left(k^{\frac{1}{4}}T^{\frac{1}{2}}\right)$. Simulations and experiments on a real storage system demonstrate that ABoB, using standard algorithms like EXP3 and Tsallis-INF, achieves lower regret and faster convergence than the flat method, up to 50% improvement in known previous setups, nonstochastic and stochastic, as well as in our settings.