# About CryoSPARC™

## What is CryoSPARC™?

CryoSPARC is a state of the art scientific software platform for cryo-electron microscopy (cryo-EM) used in research and drug discovery pipelines. CryoSPARC is used to reconstruct and visualize cryo-EM structures of biological targets including membrane proteins, viruses and complexes, from raw movies to high resolution maps. Learn more: <https://cryosparc.com/>

## What is CryoSPARC Live™?

CryoSPARC Live is an extension of CryoSPARC that delivers real-time cryo-EM data processing, quality assessment and feedback as data is collected. Learn more: <https://cryosparc.com/live>

## Licensing

CryoSPARC and CryoSPARC Live can be licensed for non-profit academic use and commercial use. Please see:

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[licensing](https://guide.cryosparc.com/licensing)
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## Citation

If you use CryoSPARC in your work, please cite as follows.

### CryoSPARC algorithms

Please cite the following papers as appropriate:

* **General CryoSPARC/CryoSPARC Live use, including preprocessing, 2D classification, Ab-initio reconstruction, Refinement:** \
  [Punjani, A., Rubinstein, J.L., Fleet, D.J. & Brubaker, M.A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nature Methods 14, 290-296 (2017).](https://www.nature.com/articles/nmeth.4169)
* **Local (per-particle) motion correction:** \
  [Rubinstein, J.L. & Brubaker, M.A. Alignment of cryo-EM movies of individual particles by optimization of image translations. Journal of Structural Biology 192 (2), 188-195 (2015).](https://www.sciencedirect.com/science/article/pii/S1047847715300459)
* **Non-uniform refinement:** \
  [Punjani, A., Zhang, H. & Fleet, D.J. Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction. Nat Methods **17,** 1214–1221 (2020).](https://www.nature.com/articles/s41592-020-00990-8)
* **3D Variability Analysis:** \
  [Punjani, A. & Fleet, D.J. 3D variability analysis: Resolving continuous flexibility and discrete heterogeneity from single particle cryo-EM. Journal of Structural Biology, Volume 213, Issue 2, 2021.\
  https://doi.org/10.1016/j.jsb.2021.107702](https://doi.org/10.1016/j.jsb.2021.107702)
* **3D Flexible Refinement:**\
  [Punjani, A. & Fleet, D.J. 3DFlex: determining structure and motion of flexible proteins from cryo-EM. Nature Methods (2023). https://doi.org/10.1038/s41592-023-01853-8](https://doi.org/10.1038/s41592-023-01853-8)

### CryoSPARC implementations

* **ResLog analysis:** \
  [Stagg, S.M., Noble, A.J., Spilman, M. & Chapman, M.S. ResLog plots as an empirical metric of the quality of cryo-EM reconstructions. Journal of Structural Biology 185 (3), 418-426 (2014).](https://www.sciencedirect.com/science/article/pii/S1047847713003377?via%3Dihub)
* **CTF refinement and aberration correction:**\
  [Zivanov, J., Nakane, T. & Scheres, S. H. W. Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in *RELION*-3.1. IUCrJ 7, 253-267 (2020). ](https://dx.doi.org/10.1107%2FS2052252520000081)

### Wrappers to third-party tools

Users should obtain their own software licenses (as applicable) for the below programs, for which wrappers are available in CryoSPARC.

* **MotionCor2:** Shawn Q. Zheng, Eugene Palovcak, Jean-Paul Armache, Yifan Cheng and David A. Agard (2016) Anisotropic Correction of Beam-induced Motion for Improved Single-particle Electron Cryo-microscopy, Nature Methods, submitted. BioArxiv: <http://biorxiv.org/content/early/2016/07/04/061960>
* **CTFFIND:** [Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. Journal of Structural Biology 192 (2), 216-221 (2015).](https://www.sciencedirect.com/science/article/pii/S1047847715300460?via%3Dihub)
* **Gctf:** Gctf: Jack (Kai) Zhang. Zhang, K. (2016). Gctf : Real-time CTF determination and correction. Journal of Structural Biology, 193(1), 1-12. <https://doi.org/10.1016/j.jsb.2015.11.003>
* **Topaz:** Bepler, T., Morin, A., Rapp, M. et al. Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs. Nat Methods 16, 1153–1160 (2019) doi:10.1038/s41592-019-0575-8 and Bepler, T., Noble, A.J., Berger, B. Topaz-Denoise: general deep denoising models for cryoEM. bioRxiv 838920 (2019) doi: <https://doi.org/10.1101/838920>
* **3DFSC:** [Tan, Y.Z., Baldwin, P.R., Davis, J.H., Williamson, J.R., Potter, C.S., Carragher, B. & Lyumkis, D. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nature Methods 14, 793-796 (2017).](http://dx.doi.org/10.1038/nmeth.4347)
* **DeepEMhancer:** R. Sanchez-Garcia, J. Gomez-Blanco, A. Cuervo et al., “DeepEMhancer: a deep learning solution for cryo-EM volume post-processing”, Communications Biology, vol. 4, no. 874, 2021. Available: 10.1038/s42003-021-02399-1.

### Dependencies

#### **cuDNN**

libcudnn.so.8 is distributed with CryoSPARC as of v3.2, pursuant to the terms of NVIDIA's Software License Agreement (SLA) for cuDNN: <https://docs.nvidia.com/deeplearning/cudnn/sla/index.html>

#### **scikit-cuda**

A modified version of scikit-cuda is included with cryosparc\_compute as of v3.2, pursuant to the scikit-cuda license terms: <https://scikit-cuda.readthedocs.io/en/latest/>&#x20;

> Redistributions of source code must retain the above copyright notice, this list of conditions and the following disclaimer. Redistributions in binary form must reproduce the above copyright notice, this list of conditions and the following disclaimer in the documentation and/or other materials provided with the distribution. Neither the name of Lev E. Givon nor the names of any contributors may be used to endorse or promote products derived from this software without specific prior written permission.&#x20;
>
> THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS “AS IS” AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE COPYRIGHT OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.

## CryoSPARC in Scientific Studies

Hundreds of structural studies have used CryoSPARC for cryo-EM data processing:

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[Google Scholar: cryoSPARC](https://scholar.google.ca/scholar?cites=6690181732944497496\&as_sdt=2005\&sciodt=0,5\&hl=en)
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## Development

CryoSPARC was originally a research project with origins at the University of Toronto in 2014. As of 2016, all research and development for CryoSPARC is done by [Structura Biotechnology Inc.](https://structura.bio/), a scientific software company based in Toronto, Canada.&#x20;

By combining our expertise in image processing, algorithm development and professional software engineering, we aim to keep CryoSPARC at the forefront of software for cryo-EM. To that end, we are constantly working on new algorithms and software features which we release on an ongoing basis. CryoSPARC's GPU-accelerated code is written entirely from scratch in-house, with exception of certain wrappers to third party tools that are clearly indicated in the documentation. Many of the algorithms in CryoSPARC are novel developments for cryo-EM image processing and links to publications can be found throughout this documentation.

### Major Version History

* CryoSPARC v5.0 was released on January 27, 2026.
* CryoSPARC v4.0 was released on October 3, 2022 and has been followed by several subsequent releases up to v4.7.1.&#x20;
* CryoSPARC v3.0 was released on December 9, 2020 and has been followed by subsequent version v3.1, v3.2 and v3.3.&#x20;
* CryoSPARC v2.0 (released August 17, 2018) was followed by a number of new releases up to v2.15.0 (released May 13, 2020).
* CryoSPARC v0.2.1 was the first public version of CryoSPARC (released February 7, 2017) and was followed by a number of new releases up to v0.6.5 (released January 12, 2018).

For release notes, see: <https://cryosparc.com/updates>

© 2026 Structura Biotechnology Inc. All rights reserved.\
CryoSPARC™ and CryoSPARC Live™ are trademarks of Structura Biotechnology Inc.