About
RELION is a leading open-source software package for electron cryo-microscopy (cryo-EM) structural biology, developed in the group of Sjors Scheres at the MRC Laboratory of Molecular Biology. The name stands for REgularised LIkelihood OptimisatioN, reflecting its core methodology: an empirical Bayesian statistical framework that enables high-resolution 3D reconstruction of macromolecular structures from cryo-EM images. The software supports two major cryo-EM workflows: single particle analysis, which resolves the structure of isolated macromolecules, and subtomogram averaging, which determines structures within their native cellular context. RELION also features on-the-fly processing, allowing researchers to analyze data in real time as it is collected at the microscope. As a cornerstone tool in the cryo-EM resolution revolution, RELION is used globally by structural biologists, biochemists, and biophysicists to study proteins, viruses, and other macromolecular complexes at near-atomic resolution. It is distributed under the GPLv2 license, making it freely available to anyone, including commercial users, who can also modify and redistribute the code. The current stable release is RELION-5.0.x. Researchers using RELION are encouraged to cite the development team's papers to support continued open development.
Key Features
- Empirical Bayesian Framework: Uses regularised likelihood optimisation (Bayesian statistics) to produce high-resolution, statistically robust 3D reconstructions from cryo-EM images.
- Single Particle Analysis: Enables determination of isolated macromolecular structures by aligning and averaging thousands of particle images to reconstruct a 3D density map.
- Subtomogram Averaging: Allows structure determination of macromolecules within their native cellular environment using cryo-electron tomography data.
- On-the-Fly Processing: Supports real-time data analysis as microscopy data is being collected, accelerating the feedback loop for data collection sessions.
- Open-Source & Free: Distributed under the GPLv2 license, RELION is freely downloadable, usable, and modifiable by anyone, including commercial organizations.
Use Cases
- Determining the near-atomic resolution 3D structure of purified proteins, protein complexes, or viruses using single particle cryo-EM analysis.
- Studying macromolecular assemblies within their native cellular environment using cryo-electron tomography and subtomogram averaging.
- Real-time on-the-fly data processing during cryo-EM data collection sessions to monitor data quality and accelerate structure determination.
- Drug discovery research requiring high-resolution structural characterization of therapeutic targets such as membrane proteins or enzyme complexes.
- Academic structural biology research and graduate-level education in cryo-EM methodology and Bayesian image processing approaches.
Pros
- Industry-Standard Tool: RELION is one of the most widely used and cited software packages in structural biology, with a large community, extensive documentation, and active development.
- Completely Free & Open Source: Licensed under GPLv2, there are no licensing costs for academic or commercial users, and the source code is fully available for inspection and modification.
- Comprehensive Workflow Coverage: Covers the full cryo-EM pipeline from motion correction and CTF estimation to 3D classification, refinement, and postprocessing.
- High-Resolution Outputs: Capable of producing near-atomic resolution reconstructions, making it suitable for drug discovery and mechanistic structural biology research.
Cons
- Steep Learning Curve: Requires significant expertise in cryo-EM methodology and computational biology; not suitable for non-specialist users without training.
- High Computational Requirements: Processing large cryo-EM datasets demands substantial HPC resources including high-memory multi-core CPUs and NVIDIA GPUs, which may be inaccessible to smaller labs.
- Primarily Linux-Focused: RELION is optimised for Linux-based HPC environments; macOS support exists but Windows is not natively supported, limiting accessibility for some users.
Frequently Asked Questions
What does RELION stand for?
RELION stands for REgularised LIkelihood OptimisatioN, reflecting its core statistical methodology based on empirical Bayesian inference.
Is RELION free to use for commercial purposes?
Yes. RELION is distributed under the GPLv2 license, which allows anyone — including commercial users — to download, use, and modify the software for free.
What types of cryo-EM data can RELION process?
RELION supports single particle cryo-EM data for isolated macromolecule structure determination, as well as cryo-electron tomography data for subtomogram averaging to study structures in their native cellular context.
What hardware is required to run RELION?
RELION is designed to run on Linux-based systems and HPC clusters. GPU acceleration via NVIDIA CUDA is strongly recommended for practical processing speeds on large datasets.
How do I cite RELION in my research?
Users are asked to cite the relevant RELION publications by Scheres et al. and other team members, as listed in the official documentation at relion.readthedocs.io.
