Dual-target function validation of single-particle selection from low-contrast cryo-electron micrographs

Weak-signal detection and single-particle selection from low-contrast micrographs of frozen hydrated biomolecules by cryo-electron microscopy (cryoEM) presents a practical challenge. Cryo-EM image contrast degrades as the size of biomolecules of structural interest decreases. When the image contrast falls into a range where the location or presence of single particles becomes ambiguous, a need arises for objective computational approaches to detect weak signal and to select and verify particles from these low-contrast micrographs. Here we propose an objective validation scheme for low-contrast particle selection using a combination of two different target functions. In an