Computational CryoET Methods

This repository is a curated list of computational cryo-ET methods!

You will find the paper and associated software for the popular algorithms used in the cryo-ET field.

The format for the item is [software link] - [Paper link] (Available in which package) and the headings may contain a link to a review paper.

• Computational CryoET Methods
• Resources
• Workflow
  • Motion correction
  • Tilt-series alignment
  • CTF estimation and correction
  • Tomogram reconstruction
  • Particle picking
  • Sub-tomogram alignment and averaging
  • Classification
  • Postprocessing
• Conventions

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Resources

Preface

• Protein Folding Problem - Great video describes the importance of understanding protein structure.
• What is cryoET - Great article that describes the cryoET.

Introduction

• Cryo-ET 101 - Deomnstrate the principles of cryo-ET using a media-rich approach with videos, animations, interactive simulation.
• Computational methods for in situ structural studies with cryogenic electron tomography - A review focus on computational methods.
• The promise and the challenges of cryo-electron tomography - A great review to start with.
• Toward high-resolution in situ structural biology with cryo-electron tomography and subtomogram averaging
• Current data processing strategies for cryo-electron tomography and subtomogram averaging
• Quantitative Cryo-Electron Tomography

Resources

• 3DEM Methods - A great wiki that collects papers or books for computational methods.
• A collective resource - A great repository that covers tomography.
• Math behind CryoEM - A great repository that collects the materials which elaborate the math behind single-particle analysis and CryoET.

Events and News

• 3DEM Events
• NRAMM Events

Software

• Scipion - An integrated platform that allows users to use a variety of methods in the same framework. [Documentation]
• Relion - A comprehensive package. [Documentation]
• nextPYP - [Documentation]
• emClarity - [Documentation]
• IMDO
• EMAN2
• Warp
• Dynamo
• AITom
• PyTom
• TomoBEAR
• STOPGAP - See [Documentation]

Workflow

Import Data

1. From EMPIAR or EMDB.

2. From tutorial data set.

• https://scipion-em.github.io/docs/release-3.0.0/docs/user/user-documentation.html#tomography-tutorials

3. Generate simulation data
   • cryoSRPNT
   • PolNet - Simulating the cellular context in synthetic datasets for cryo-electron tomography
   • faket - Simulating the cellular context in synthetic datasets for cryo-electron tomography
   • https://github.com/MPI-Dortmund/tem-simulator-scripts
   • MEPSi - MEPSi: A tool for simulating tomograms of membrane-embedded proteins
   • https://github.com/xulabs/aitom/blob/master/doc/tutorials/004_simulate_whole_tomogram.py
   • https://github.com/xulabs/aitom/blob/master/doc/tutorials/003_simulate_subtomogram.py
   • https://github.com/anmartinezs/pyseg_system/blob/master/code/pyorg/scripts/synthetic/gen_microsomes.py
   • https://www.shrec.net/cryo-et/
   • parakeet - Parakeet: A digital twin software pipeline to assess the impact of experimental parameters on tomographic reconstructions for cryo-electron tomography

Image Formation model

1. TEM Simulator - Simulation of transmission electron microscope images of biological specimens

2. InSilicoTEM - Image formation modeling in cryo-electron microscopy

3. CisTEM_Simulate - Cryo-TEM simulations of amorphous radiation-sensitive samples using multislice wave propagation

Motion correction

1. MotionCorr2 - MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy (Use in Relion)
2. Unblur - Measuring the optimal exposure for single particle cryo-EM using a 2.6 Å reconstruction of rotavirus VP6
3. Alignparts - Alignment of cryo-EM Movies of Individual Particles by Optimization of Image Translations
4. FlexAlign - FlexAlign: An Accurate and Fast Algorithm for Movie Alignment in Cryo-Electron Microscopy - (Use in Scipion)

Tilt-series alignment

Fiducial based

1. IMOD - Automated tilt series alignment and tomographic reconstruction in IMOD (Use in IMOD)
2. Dynamo - Automated fiducial-based alignment of cryo-electron tomography tilt series in Dynamo (Use in Dynamo)

Fiducialless

1. AreTomo - AreTomo: An integrated software package for automated marker-free, motion-corrected cryo-electron tomographic alignment and reconstruction
2. TomoAlign - Cryo-tomography tilt-series alignment with consideration of the beam-induced sample motion
3. Xmipp - A deep learning approach to the automatic detection of alignment errors in cryo-electron tomographic reconstructions (Use in Xmipp)

Detect fiducial marker

1. MarkerDetector - MarkerDetector: A method for robust fiducial marker detection in electron micrographs using wavelet-based template (Use in IMOD)

CTF estimation and correction

1. CTFFIND4 - CTFFIND4: Fast and accurate defocus estimation from electron micrographs ( Use in CisTEM)
2. gCTF - Gctf: Real-time CTF determination and correction
3. ctfplotter- CTF determination and correction for low dose tomographic tilt series (Use in IMOD)
4. novaCTF - Efficient 3D-CTF correction for cryo-electron tomography using NovaCTF improves subtomogram averaging resolution to 3.4 Å
5. Warp
6. M - Multi-particle cryo-EM refinement with M visualizes ribosome-antibiotic complex at 3.5 Å inside cells. [Video]
7. Ctfplotter - Accurate, automatic determination of astigmatism and phase with Ctfplotter in IMOD (Use in IMOD)

Tomogram reconstruction

1. A Survey of the Use of Iterative Reconstruction Algorithms in Electron Microscopy
2. Tomo3D -Tomo3D 2.0 – Exploitation of Advanced Vector eXtensions (AVX) for 3D reconstruction

Denoising tomogram

1. SC-Net - Self-Supervised Cryo-Electron Tomography Volumetric Image Restoration from Single Noisy Volume with Sparsity Constraint
2. CryoCARE - Content-aware image restoration for electron microscopy
3. Topaz - Topaz-Denoise: general deep denoising models for cryoEM
4. TomoEED - TomoEED: fast edge-enhancing denoising of tomographic volumes
5. DUAL - DUAL: deep unsupervised simultaneous simulation and denoising for cryo-electron tomography (Use in AITom)
6. REST - A method for restoring signals and revealing individual macromolecule states in cryo-ET, REST
7. CCPEM Denoiser

Particle picking

1. DeePiCt - Convolutional networks for supervised mining of molecular patterns within cellular context
2. DeepFinder - Deep learning improves macromolecule identification in 3D cellular cryo-electron tomograms
3. Cryolo - SPHIRE-crYOLO is a fast and accurate fully automated particle picker for cryo-EM. [Video]
4. PySeg - Template-free detection and classification of membrane-bound complexes in cryo-electron tomograms
5. TomoTwin - TomoTwin: generalized 3D localization of macromolecules in cryo-electron tomograms with structural data mining
6. pytom-match-pick - Extensive Angular Sampling Enables the Sensitive Localization of Macromolecules in Electron Tomograms (Use in PyTom)
7. TARDIS - Automated Segmentation of 3D Cytoskeletal Filaments from Electron Micrographs with TARDIS
8. TomoTwin - TomoTwin: generalized 3D localization of macromolecules in cryo-electron tomograms with structural data mining
9. TomoNet - TomoNet: A streamlined cryogenic electron tomography software pipeline with automatic particle picking on flexible lattices
10. cet_pick_size - Accurate size-based protein localization from cryo-ET tomograms (Use in nextPYP)
11. PyTME - PyTME (Python Template Matching Engine): A fast, flexible, and multi-purpose template matching library for cryogenic electron microscopy data

Sub-tomogram alignment and averaging

1. emClarity - emClarity: software for high-resolution cryo-electron tomography and subtomogram averaging
2. Dynamo - Dynamo: A flexible, user-friendly development tool for subtomogram averaging of cryo-EM data in high-performance computing environments
3. IsoNet - Isotropic reconstruction for electron tomography with deep learning

Classification

1. AITom - High-throughput cryo-ET structural pattern mining by unsupervised deep iterative subtomogram clustering
2. TomoDRGN - Learning structural heterogeneity from cryo-electron sub-tomograms with tomoDRGN
3. CryoDRGN-ET - Deep reconstructing generative networks for visualizing dynamic biomolecules inside cells

Post-processing

Local resolution

1. Monotomo - Measurement of local resolution in electron tomography

Visualization

1. Chimera - UCSF Chimera--a Visualization System for Exploratory Research and Analysis
2. ChimeraX - UCSF ChimeraX: Meeting modern challenges in visualization and analysis
3. ArtiaX
4. blik - Blik is an extensible 3D visualisation tool for the annotation and analysis of cryo-electron tomography data
5. Colabseg - ColabSeg: An interactive tool for editing, processing, and visualizing membrane segmentations from cryo-ET data

Conventions

3DEM Convention

• 3DEM Conventions