Seitz, Evan / Frank, Joachim / Schwander, Peter. Beyond ManifoldEM: geometric relationships between manifold embeddings of a continuum of 3D molecular structures and their 2D projections. 2023. Digital Discovery, Vol. 2, p. 702-717
ManifoldEM is an established method of geometric machine learning developed to extract information on conformational motions of molecules from their projections obtained by cryogenic electron microscopy (cryo-EM). In a previous work, in-depth analysis of the properties of manifolds obtained for simulated ground-truth data from molecules exhibiting domain motions has led to improvements of this method, as demonstrated in selected applications of single-particle cryo-EM. In the present work this analysis has been extended to investigate the properties of manifolds constructed by embedding data from synthetic models represented by atomic coordinates in motion, or three-dimensional density maps from biophysical experiments other than single-particle cryo-EM, with extensions to cryo-electron tomography and single-particle imaging with a X-ray free-electron laser. Our theoretical analysis revealed interesting relationships between all these manifolds, which can be exploited in future work.