Tracing Filaments in Simulated 3D Cryo-Electron Tomography Maps Using a Fast Dynamic Programming Algorithm.

We propose a fast, dynamic programming-based framework for tracing actin filaments in 3D maps of subcellular components in cryo-electron tomography. The approach can identify high-density filament segments in various orientations, but it takes advantage of the arrangement of actin filaments within cells into more or less tightly aligned bundles. Assuming that the tomogram can be rotated such that the filaments can be oriented to be directed in a dominant direction (i.e., the , , or axis), the proposed framework first identifies local seed points that form the origin of candidate filament segments (CFSs), which are then grown from the seeds using a fast dynamic programming algorithm. The CFS length can be tuned to the nominal resolution of the tomogram or the separation of desired features, or it can be used to restrict the curvature of filaments that deviate from the overall bundle direction. In subsequent steps, the CFSs are filtered based on backward tracing and path density analysis. Finally, neighboring CFSs are fused based on a collinearity criterion to bridge any noise artifacts in the 3D map that would otherwise fractionalize the tracing. We validate our proposed framework on simulated tomograms that closely mimic the features and appearance of experimental maps.