Robust target detection with 2DTM p-value

Scatter plots compare conventional 2DTM detection thresholds with the p-value approach, highlighting true positives. — A new detection score helps separate molecular signals from noise.

Detecting smaller targets by 2D template matching (2DTM) is difficult because the detected signal depends on the molecular weight of the target. Low-resolution contrast can be a reliable indicator of a target, but is down-weighted in the standard 2DTM workflow. We address these challenges by developing a new statistical metric — the 2DTM p-value — that improves the detection of several previously challenging targets, including a 193 kDa clathrin monomer.

The 2DTM p-value is particularly useful for detecting targets of 50 kDa and smaller, and for reliably detecting rare targets that require higher detection thresholds to suppress false positives.

Publication: A new statistical metric for robust target detection in cryo-EM using 2D template matching · IUCrJ (2025).