End-to-end reconstruction for cryo electron ptychographic single-particle analysis

End2EndPtychoSPA improves cryo-ptycho single-particle 3D reconstruction on simulated haemoglobin, reaching 3.22 Å resolution (FSC 0.5) versus 3.41 Å for the sequential route.

• Why it matters: Sequential cryo-ptycho SPA pipelines reconstruct 2D phase micrographs first, then use conventional SPA software, which can limit accuracy and propagate errors into 3D potential maps.
• What they did: The authors fit a 3D electrostatic potential volume and particle poses directly to 4D-STEM diffraction data using an end-to-end differentiable multislice forward model, including a learnable vitreous-ice layer.
• The result: On apoferritin (11,552 particles), End2EndPtychoSPA improves agreement with an external atomic model and shifts the unmasked half-map FSC 0.143 crossing from 6.83 Å to 5.99 Å, while not improving on T20S, TMV, or Phi92.

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