Resources · Data-Processing Pipeline

Cryo-ET Processing Pipeline

The tomography counterpart to our single-particle workflow: taking cells from raw tilt series to subtomogram averages that reveal macromolecular organization in its native context. Adapted from the SBGrid NIH R25 Train-the-Trainer CryoET curriculum, co-led by our lab.

Cryo-electron tomography
Cloud-based (SBCloud)
In-cell & native-context imaging

Workflow steps

A complete tomography workflow from raw tilt-series data through subtomogram averaging and presentation of results — the same sequence taught in SBGrid's two-day CryoET Data Processing curriculum.

1

Cryo-ET workflow overview

Review the full tomography pipeline and project organization before processing, since cryo-ET workflows combine several specialized tools in sequence.

2

Tilt-series preprocessing & alignment

Correct motion in each tilt image, order the tilt series, and align images to a common tilt axis using fiducial or patch-tracking methods.

3

Tomogram reconstruction

Back-project the aligned tilt series into a 3D tomographic volume representing the imaged cellular region.

4

Denoising & missing-wedge correction

Apply denoising to improve contrast and use missing-wedge correction or restoration to reduce reconstruction artifacts from limited tilt range.

5

Segmentation & particle identification

Segment cellular features of interest (e.g. membranes, organelles) and identify candidate particles for further averaging.

6

Particle export

Export particle coordinates and sub-volumes from the tomogram for downstream subtomogram averaging.

7

Subtomogram averaging

Align and average many copies of the same particle extracted from tomograms to boost signal-to-noise and resolve higher-resolution structure.

8

Figure generation & presentation

Generate segmentation renderings and averaged-structure figures, and prepare final results for presentation — mirroring each workshop's final participant presentations.

Worked training example

Milled Saccharomyces cerevisiae cells — SBGrid Data Bank 1255

The SBGrid CryoET Train-the-Trainer curriculum runs this pipeline on a public training dataset of tilt-series from milled Saccharomyces cerevisiae cells, made available through the SBGrid Data Bank (doi:10.15785/sbgrid/1255) by the Raunser Laboratory, Max Planck Institute of Molecular Physiology. The dataset shows mitochondria, nuclear envelopes, lipid bodies, smooth endoplasmic reticulum, and other intracellular components — roughly 37 GB of authentic in-cell tomography data.

References

Primary sources for this workflow. Each link goes to the original resource so you can confirm details directly.

01
SBGrid NIH R25 Training — CryoEM & CryoET Data Processing WorkshopsProgram overview and CryoET curriculum topics (SBGrid Consortium, Harvard Medical School).
02
SBGrid Data Bank — Dataset 1255Public CryoET training dataset: milled S. cerevisiae cells, ~37 GB, Raunser Laboratory (MPI Molecular Physiology).
03
doi:10.15785/sbgrid/1255Persistent identifier for the training dataset.
04
CryoET training workflow webinarRecorded walkthrough of the tomography workflow (SBGrid).
05
SBCloudCloud-based training environment used to run the pipeline (curated software, CPU/GPU, storage, visualization).