Exploiting prior knowledge about biological macromolecules in cryo-EM structure determination.

Three-dimensional reconstruction of the electron-scattering potential of biological macromolecules from electron cryo-microscopy (cryo-EM) projection images is an ill-posed problem. The most popular cryo-EM software solutions to date rely on a regularization approach that is based on the prior assumption that the scattering potential varies smoothly over three-dimensional space. Although this approach has been hugely successful in recent years, the amount of prior knowledge that it exploits compares unfavorably with the knowledge about biological structures that has been accumulated over decades of research in structural biology.

On Learned Operator Correction in Inverse Problems.

We discuss the possibility of learning a data-driven explicit model correction for inverse problems and whether such a model correction can be used within a variational framework to obtain regularized reconstructions. This paper discusses the conceptual difficulty of learning such a forward model correction and proceeds to present a possible solution as a forward-adjoint correction that explicitly corrects in both data and solution spaces. We then derive conditions under which solutions to the variational problem with a learned correction converge to solutions obtained with the correct operator.