CryoTracer: A Synthetic-to-Real System for Filament Instance Tracing in Cryo-EM

Particle picking in cryo-electron microscopy is commonly formulated as an object-detection problem in which individual particles are represented by bounding boxes, a natural representation for globular particles but a poor match for filaments that can extend across an entire micrograph. Existing methods reconstruct filament trajectories by linking local predictions in a separate post-processing stage, decoupling detection from instance formation and creating potential ambiguities at gaps and crossings. Directly preserving filament identity is particularly useful for polymorphic specimens, where segments originating from the same filament should remain associated. However, learning such instance-level representations is challenging because expert centerline annotations are scarce and costly to obtain. We introduce CryoTracer, a synthetic-to-real framework that addresses this limitation through procedural micrograph generation, transformer-based polyline prediction, and specimen-specific fine-tuning. Procedural pretraining exposes the model to diverse filament geometries, intersections, and imaging conditions before adaptation using a limited number of fully annotated experimental micrographs. CryoTracer represents filaments as ordered centerline polylines and optimizes their geometry using an orientation-invariant discrete Fréchet objective, enabling consistent learning regardless of tracing direction. Evaluation on established and newly expert-annotated datasets shows that CryoTracer improves instance-level filament recovery over existing particle-detection approaches. Complementary metrics distinguish regional coverage from complete-instance recovery, providing a more detailed assessment of filament-tracing performance. Together, these results establish end-to-end polyline prediction as a practical alternative to detection-and-linking pipelines for recovering complete filament instances with limited micrograph annotation budgets.