foldSeekR

Description

foldSeekR is an R package designed to streamline protein structure predictions via AlphaFold (https://alphafold.ebi.ac.uk/) and architecture comparisons via FoldSeek (https://www.foldseek.com). foldSeekR uses Uniprot accession ID’s or FASTA files or strings to search structure similarities on AlphaFold. It uses FoldSeek to query the AlphaFold database for the most similar protein architectures to the protein structure of interest. It provides visualization of the protein of interest and the similar proteins with highlighted regions similar to the target protein.

foldSeekR was developed using:

R version 4.4.1 (2024-06-14)
Platform: aarch64-apple-darwin20
Running under: macOS Sonoma 14.6.1

Installation

To install the latest version of the package:

require("devtools")
devtools::install_github("bellabr/foldSeekR", build_vignettes = TRUE)
library("foldSeekR")

To run the shinyApp:

runFoldSeekR()

Overview

ls("package:foldSeekR")
browseVignettes("foldSeekR")

foldSeekR contains 3 functions in the current version.

• pull_prediction for pulling protein architecture prediction information from AlphaFold including sequential information.

• pull_summary for pulling protein summary information from AlphaFold including Uniprot information and structural information.

• pull_url for retrieving the links to downloadable data files (PDB, CIF, or mmCIF) for the specified accession.

• available_databases for retrieving the databases available to be searched for structure similarity.

• ticket for submitting a FoldSeek job and retrieving a ticket.

• status for checking the status of the job submission.

• foldseek for submitting a job, handling the ticket, and retrieving information from the search query.

• cache_top_hits for caching a number of top hits with respect to sequence similarity for later use.

• clear_cache for clearing the cache for a given accession thread.

• visualize_prediction for producing an interactive and colourful visualization of the protein of interest.

• visualize_foldseeks for producing an interactive and colourful visualization of the protein of interest compared to the cached top hits for similar proteins in structure. The visualizations are side-by-side and interact together, in addition to being colour-coded by each region of similarity to the target protein of interest.

Refer to package vignettes for more details.

An image outlining the workflow of foldSeekR is illustrated below.

Contributions

The author of the package is Annabella Bregazzi.

The author wrote the pull_prediction function, which makes use of httr2, jsonlite.

The author wrote the pull_summary function, which makes use of httr2, jsonlite.

The author wrote the pull_url function, which makes use of httr2, jsonlite.

The author wrote the available_databases function, which makes use of httr2, jsonlite.

The author wrote the ticket function, which makes use of httr2, jsonlite, curl.

The author wrote the status function, which makes use of httr2, jsonlite.

The author wrote the foldseek function, which makes use of httr2, jsonlite.

The author wrote the cache_top_hits function, which makes use of BiocFileCache.

The author wrote the clear_cache function, which makes use of BiocFileCache.

The author wrote the visualize_prediction function, which makes use of BiocFileCache, r3dmol, bio3d.

The author wrote the visualize_foldseeks function, which makes use of BiocFileCache, r3dmol, bio3d.

No generative AI tools were used in the development of this package.

References

• Barrio-Hernandez, I., Yeo, J., Jänes, J., Mirdita, M., Gilchrist, C.L.M., Wein, T., Varadi, M., Velanka, S., Beltrao, P., and Steinegger, M (2023). Clustering predicted structures at the scale of the known protein universe. Nature 622: 637-645. https://doi.org/10.1038/s41586-023-06510-w.

• Grant B, Rodrigues A, ElSawy K, McCammon J, Caves L (2006). “Bio3D: An R package for the comparative analysis of protein structures.” Bioinformatics, 22, 2695–2696.

• Jumper, J. et al. “Highly accurate protein structure prediction with AlphaFold.” Nature, 596, pages 583–589 (2021). DOI: 10.1038/s41586-021-03819-2.

• van Kempen, M., Kim, S.S., Tumescheit, C., Mirdita, M., Lee, J., Gilchrist, C.L.M., Söding, J., and Steinegger, M (2024). Fast and accurate protein structure search with Foldseek. Nature Biotechnology 42: 243-246. https://doi.org/10.1038/s41587-023-01773-0.

• Kim, W., Mirdita, M., Karin, E.L., Gilchrist, C., Schweke, H., Söding, J., Levy, E., and Steinegger, M. (2024). Rapid and Sensitive Protein Complex Alignment with Foldseek-Multimer. bioRxiv 2024.04.14.589414. https://www.biorxiv.org/content/10.1101/2024.04.14.589414v1.

• Ooms J (2024). curl: A Modern and Flexible Web Client for R. R package version 6.0.2, https://github.com/jeroen/curl.

• Ooms J (2014). “The jsonlite Package: A Practical and Consistent Mapping Between JSON Data and R Objects.” arXiv:1403.2805 [stat.CO]. https://arxiv.org/abs/1403.2805.

• Shepherd L, Morgan M (2024). BiocFileCache: Manage Files Across Sessions. R package version 2.14.0.

• Su W, Johnston B (2023). r3dmol: Create Interactive 3D Visualizations of Molecular Data. R package version 0.2.0, https://github.com/swsoyee/r3dmol.

• Varadi, M. et al. “AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models.” Nucleic Acids Research, 50(D1), pages D439–D444 (2021). DOI: 10.1093/nar/gkab1061

• Varadi, M. et al. “AlphaFold Protein Structure Database in 2024: Providing structure coverage for over 214 million protein sequences.” Nucleic Acids Research, gkad1011 (2023). DOI: 10.1093/nar/gkad1011

• Wickham H (2024). httr2: Perform HTTP Requests and Process the Responses. R package version 1.0.6.9000, , https://github.com/r-lib/httr2.

Acknowledgments

This package was developed as part of an assessment for 2024 BCB410H: Applied Bioinformatics course at the University of Toronto, Toronto, CANADA. foldSeekR welcomes issues, enhancement requests, and other contributions. To submit an issue, use the GitHub issues.