Cryo-EM density maps adjustment for subtraction, consensus and sharpening

Electron cryomicroscopy (cryo-EM) has emerged as a powerful structural biology instrument to solve near-atomic three-dimensional structures. Despite the fast growth in the number of density maps generated from cryo-EM data, comparison tools among these reconstructions are still lacking. Current proposals to compare cryo-EM data derived volumes perform map subtraction based on adjustment of each volume grey level to the same scale. We present here a more sophisticated way of adjusting the volumes before comparing, which implies adjustment of grey level scale and spectrum energy, but keeping phases intact inside a mask and imposing the results to be strictly positive. The adjustment that we propose leaves the volumes in the same numeric frame, allowing to perform operations among the adjusted volumes in a more reliable way. This adjustment can be a preliminary step for several applications such as comparison through subtraction, map sharpening, or combination of volumes through a consensus that selects the best resolved parts of each input map. Our development might also be used as a sharpening method using an atomic model as a reference. We illustrate the applicability of this algorithm with the reconstructions derived of several experimental examples. This algorithm is implemented in Xmipp software package and its applications are user-friendly accessible through the cryo-EM image processing framework Scipion.