README.md

Tox21Enricher-Shiny

Tox21Enricher-Shiny is a web application built using the Shiny framework for R. It performs PubChem enrichment analysis on a set or sets of chemicals included in the the Tox21 chemical dataset, and it is being devloped in collaboration with the NIEHS as part of their suite of Tox21-related tools.

The user manual for Tox21Enricher-Shiny can be found in the docs/ subdirectory. Additional documentation for acquiring, configuring, and deploying Tox21Enricher-Shiny can also be found in the docs/ subdirectory.

The Hur Lab at the University of North Dakota School of Medicine and Health Sciences hosts an instance of the Tox21Enricher-Shiny application here and an instance of the API here.

The Tox21Enricher database may be downloaded in its entirety here. (You may need to right-click, copy the link address, and paste it in a new window to download.)

An empty copy of Tox21Enricher's "queue" database used during processing of enrichment requests can be downloaded here. (You may need to right-click, copy the link address, and paste it in a new window to download.)

A Docker Compose project to deploy Tox21Enricher-Shiny on your own machine can be found here.

Tox21Enricher-Shiny is an updated version of and replaces the original Tox21 Enricher (Now called Tox21Enricher-Grails). The Grails version is hosted at The UND SMHS hurlab server and its original publication can be found at doi:10.1002/minf.201700129.

Usage

Chemicals are specified directly via their corresponding CASRN or indirectly with a SMILES/InChI string upon which a substructure search is executed. Once chemicals containing the given chemical string(s) are identified, CASRNs are used and enrichment proceeds as if the system was given CASRN input originally. Enrichment is then performed on the CASRNs.

After performing enrichment, the results are displayed (heatmap images per set, .gct, .xls, .txt files, cluster and chart full heatmaps) along with an option to view the cluster and chart full heatmaps visualized as networks. In the networks displayed, two nodes with a connecting edge indicate two annotations that have a statistically significant connection.

Specifications and Dependencies

The following packages, libraries, and tools are required to build Tox21Enricher-Shiny from source. Similar operating systems and versions of packages different from those specified may work, but were not tested and are not guaranteed to perform correctly:

Dependency	Version	Additional Notes	Citation
PostgreSQL	11.8	Database management	The PostgreSQL Global Development Group (2023). PostgreSQL: The World's Most Advanced Open Source Relational Database. https://www.postgresql.org/
RDKit		Postgres database extension	RDKit: Open-source cheminformatics. https://www.rdkit.org

R and R Packages

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• graphics-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
• grDevices-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
• grid-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
• gridExtra-2.3: Auguie B (2017). gridExtra: Miscellaneous Functions for "Grid" Graphics. R package version 2.3, https://CRAN.R-project.org/package=gridExtra.
• gtable-0.3.3: Wickham H, Pedersen T (2023). gtable: Arrange 'Grobs' in Tables. R package version 0.3.3, https://CRAN.R-project.org/package=gtable.
• hms-1.1.3: Müller K (2023). hms: Pretty Time of Day. R package version 1.1.3, https://CRAN.R-project.org/package=hms.
• htmltools-0.5.5: Cheng J, Sievert C, Schloerke B, Chang W, Xie Y, Allen J (2023). htmltools: Tools for HTML. R package version 0.5.5, https://CRAN.R-project.org/package=htmltools.
• htmlwidgets-1.6.2: Vaidyanathan R, Xie Y, Allaire J, Cheng J, Sievert C, Russell K (2023). htmlwidgets: HTML Widgets for R. R package version 1.6.2, https://CRAN.R-project.org/package=htmlwidgets.
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• iterators-1.0.14: Analytics R, Weston S (2022). iterators: Provides Iterator Construct. R package version 1.0.14, https://CRAN.R-project.org/package=iterators.
• jsonlite-1.8.7: 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.
• lambda.r-1.2.4: Rowe BLY (2019). lambda.r: Modeling Data with Functional Programming. R package version 1.2.4, https://CRAN.R-project.org/package=lambda.r.
• later-1.3.1: Chang W, Cheng J (2023). later: Utilities for Scheduling Functions to Execute Later with Event Loops. R package version 1.3.1, https://CRAN.R-project.org/package=later.
• lazyeval-0.2.2: Wickham H (2019). lazyeval: Lazy (Non-Standard) Evaluation. R package version 0.2.2, https://CRAN.R-project.org/package=lazyeval.
• lifecycle-1.0.3: Henry L, Wickham H (2022). lifecycle: Manage the Life Cycle of your Package Functions. R package version 1.0.3, https://CRAN.R-project.org/package=lifecycle.
• listenv-0.9.0: Bengtsson H (2022). listenv: Environments Behaving (Almost) as Lists. R package version 0.9.0, https://CRAN.R-project.org/package=listenv.
• magrittr-2.0.3: Bache S, Wickham H (2022). magrittr: A Forward-Pipe Operator for R. R package version 2.0.3, https://CRAN.R-project.org/package=magrittr.
• methods-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
• mime-0.12: Xie Y (2021). mime: Map Filenames to MIME Types. R package version 0.12, https://CRAN.R-project.org/package=mime.
• munsell-0.5.0: Wickham C (2018). munsell: Utilities for Using Munsell Colours. R package version 0.5.0, https://CRAN.R-project.org/package=munsell.
• parallel-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
• parallelly-1.36.0: Bengtsson H (2023). parallelly: Enhancing the 'parallel' Package. R package version 1.36.0, https://CRAN.R-project.org/package=parallelly.
• pillar-1.9.0: Müller K, Wickham H (2023). pillar: Coloured Formatting for Columns. R package version 1.9.0, https://CRAN.R-project.org/package=pillar.
• pkgconfig-2.0.3: Csárdi G (2019). pkgconfig: Private Configuration for 'R' Packages. R package version 2.0.3, https://CRAN.R-project.org/package=pkgconfig.
• R6-2.5.1: Chang W (2021). R6: Encapsulated Classes with Reference Semantics. R package version 2.5.1, https://CRAN.R-project.org/package=R6.
• RColorBrewer-1.1.3: Neuwirth E (2022). RColorBrewer: ColorBrewer Palettes. R package version 1.1-3, https://CRAN.R-project.org/package=RColorBrewer.
• Rcpp-1.0.9:
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• registry-0.5.1: Meyer D (2019). registry: Infrastructure for R Package Registries. R package version 0.5-1, https://CRAN.R-project.org/package=registry.
• rlang-1.1.1: Henry L, Wickham H (2023). rlang: Functions for Base Types and Core R and 'Tidyverse' Features. R package version 1.1.1, https://CRAN.R-project.org/package=rlang.
• rstudioapi-0.15.0: Ushey K, Allaire J, Wickham H, Ritchie G (2023). rstudioapi: Safely Access the RStudio API. R package version 0.15.0, https://CRAN.R-project.org/package=rstudioapi.
• scales-1.2.1: Wickham H, Seidel D (2022). scales: Scale Functions for Visualization. R package version 1.2.1, https://CRAN.R-project.org/package=scales.
• seriation-1.5.1:
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• stats-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
• stringi-1.7.8: Gagolewski M (2022). “stringi: Fast and portable character string processing in R.” Journal of Statistical Software, 103(2), 1-59. doi:10.18637/jss.v103.i02 https://doi.org/10.18637/jss.v103.i02.
• tidyselect-1.2.0: Henry L, Wickham H (2022). tidyselect: Select from a Set of Strings. R package version 1.2.0, https://CRAN.R-project.org/package=tidyselect.
• timechange-0.2.0: Spinu V (2023). timechange: Efficient Manipulation of Date-Times. R package version 0.2.0, https://CRAN.R-project.org/package=timechange.
• tools-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
• TSP-1.2.4:
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• tzdb-0.4.0: Vaughan D (2023). tzdb: Time Zone Database Information. R package version 0.4.0, https://CRAN.R-project.org/package=tzdb.
• utf8-1.2.2: Perry PO (2021). utf8: Unicode Text Processing. R package version 1.2.2, https://CRAN.R-project.org/package=utf8.
• utils-4.2.3: R Core Team (2023). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/.
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• yaml-2.3.6: Garbett SP, Stephens J, Simonov K, Xie Y, Dong Z, Wickham H, Horner J, reikoch, Beasley W, O'Connor B, Warnes GR, Quinn M, Kamvar ZN (2022). yaml: Methods to Convert R Data to YAML and Back. R package version 2.3.6, https://CRAN.R-project.org/package=yaml.

Additionally, building the project images using Docker or running the project using Docker Compose requires the following:

Dependency	Version	Additional Notes	Citation
Docker	23.0.1		https://www.docker.com/
Docker Compose	1.25.0	Not required but recommended for local deployment	https://docs.docker.com/compose/

Parallel processing is not supported if running the API directly on a Windows machine. Parallel processing also needs to allocate at least 2000 MiB or 2 GiB of memory to function properly.

The development machine for Tox21Enricher-Shiny uses 64-bit Linux, so that is the recommended architecture. Other builds may not perform as expected.

Credit

If using this work, please cite the following publication(s):

• Combs P, Erickson J, Hsieh J-H, Guo K, Nolte S, Schmitt C, Auerbach S and Hur J (2023). Tox21Enricher-Shiny: an R Shiny application for toxicity functional annotation analysis. Front. Toxicol. 5:1147608. doi: 10.3389/ftox.2023.1147608.
• Combs P, Erickson J, Hsieh J-H, Guo K, Nolte S, Schmitt C, Auerbach S and Hur J (2023). Corrigendum: Tox21Enricher-Shiny: an R Shiny application for toxicity functional annotation analysis. Front. Toxicol. 5:1278066. doi: 10.3389/ftox.2023.1278066.