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Free, publicly-accessible full text available November 1, 2025
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As experiments continue to increase in size and scope, a fundamental challenge of subsequent analyses is to recast the wealth of information into an intuitive and readily interpretable form. Often, each measurement conveys only the relationship between a pair of entries, and it is difficult to integrate these local interactions across a dataset to form a cohesive global picture. The classic localization problem tackles this question, transforming local measurements into a global map that reveals the underlying structure of a system. Here, we examine the more challenging bipartite localization problem, where pairwise distances are available only for bipartite data comprising two classes of entries (such as antibody-virus interactions, drug-cell potency, or user-rating profiles). We modify previous algorithms to solve bipartite localization and examine how each method behaves in the presence of noise, outliers, and partially observed data. As a proof of concept, we apply these algorithms to antibody-virus neutralization measurements to create a basis set of antibody behaviors, formalize how potently inhibiting some viruses necessitates weakly inhibiting other viruses, and quantify how often combinations of antibodies exhibit degenerate behavior.more » « less
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The number of noisy images required for molecular reconstruction in single-particle cryoelectron microscopy (cryo-EM) is governed by the autocorrelations of the observed, randomly oriented, noisy projection images. In this work, we consider the effect of imposing sparsity priors on the molecule. We use techniques from signal processing, optimization, and applied algebraic geometry to obtain theoretical and computational contributions for this challenging nonlinear inverse problem with sparsity constraints. We prove that molecular structures modeled as sums of Gaussians are uniquely determined by the second-order autocorrelation of their projection images, implying that the sample complexity is proportional to the square of the variance of the noise. This theory improves upon the nonsparse case, where the third-order autocorrelation is required for uniformly oriented particle images and the sample complexity scales with the cube of the noise variance. Furthermore, we build a computational framework to reconstruct molecular structures which are sparse in the wavelet basis. This method combines the sparse representation for the molecule with projection-based techniques used for phase retrieval in X-ray crystallography.more » « less