Table 1:
Selected freely available read-across tools - Adapted from Patlewicz et al. (2017)
| AIM | Toxmatch | Ambit | OECD QSAR Toolbox | CBRA | ToxRead | CIIPro | GenRAa | |
|---|---|---|---|---|---|---|---|---|
| Development timeline | Java based version is dated 2012. Initial development of web version was 2005. | First public version released in Dec 2006 | Original AMBIT tool was developed in 2004-2005 | Proof of concept released in 2008 | Implementation of the Low et al., (2013) article | Implementation of Gini et al., (2014) | Implementation described in Russo et al., (2017) | Released August 2018, described in Helman et al. (2019) |
| Type of Tool | Standalone | Standalone | Web-based and standalone | Standalone and client/server | Standalone | Standalone | Web-based | Web-based via the EPA CompTox Chemicals Dashboard |
| Latest Version and any Updates | 1.01 (Nov 2013) Static | 1.07 (Jan 2009) Static | 3.0.3 (2013-2015) Ongoing | 4.3 (January 2019) Ongoing | 0.75 (2013) First release | 0.11 BETA (2014) Ongoing | First release | First release (Aug 2018) |
| Developed by | SRC, Inc. | IDEAconsult Ltd. | IDEAconsult Ltd. | Laboratory of Mathematical Chemistry, University Asen Zlatarov | Fourches Lab, North Carolina State University | Istituto di Ricerche Farmacologiche Mario Negri | Zhu Research Group, Rutgers University | NCCT, EPA |
| Available from | https://www.epa.gov/tsca-screening-tools/analog-identification-methodology-aim-tool | https://eurl-ecvam.jrc.ec.europa.eu/laboratories-research/predictive_toxicology/qsar_tools/toxmatch | http://cefic-lri.org/lri_toolbox/ambit/ | www.qsartoolbox.org | http://www.fourches-laboratory.com/software | http://www.toxread.eu/ | http://ciipro.rutgers.edu/ | https://comptox.epa.gov/dashboard |
| Accepted Chemical Input | CAS, name, SMILES, structure drawing/import | CAS, name, SMILES, InChI | Name, SMILES, InChI | CAS, name, SMILES, structure drawing, structure data file (sdf) | Mol file, descriptors as txt | SMILES | PubChem CID, CAS, IUPAC, SMILES, InChI | Linked to the DSSTox inventory |
| Endpoint Coverage | N/A | Any; based on user input | IUCLIDb 5-supported endpoints (43 total) | Any, per available regulatory endpoints | Any; based on user input | Mutagenicity and bioconcentration factor | Any; based on user input | Repeat-dose toxicity endpoints covered in ToxRefDB v1.0 |
| Analog Identification Approach | Fragment matching | Distance and correlation-based similarity indices based on descriptors or fingerprints | Substructure or similarity searching using structure, name, SMILES, InChI | Category definition followed by subcategorizations | Tanimoto distance using chemical and biological descriptors | VEGA similarity algorithm | Weighted estimated biological similarity | Jaccard similarity index based on different chemical fingerprints – Morgan, Torsion, Chemotype |
| Neighbor Selection | Automatic | Automatic | Manual | Automatic + manual filter | Automatic | Automatic | Automatic + manual filter | Automatic + manual filter |
| Data Source | Tool provides inventory index | User- or tool provided | User- or tool provided | User- or tool provided | User-provided | Tool-provided (EU ANTARES project) | User-provided; tool provides PubChem in vitro data | Tool-provided (ToxRef DB) |
| Quantitative vs Qualitative | N/A | Both | Qualitative (user-determined) | Both | Qualitative | Qualitative for mutagenicity, quantitative for bioconcentration factor | Qualitative | Quantitative binary predictions with measures of confidence of toxicity effects within the different study types |
| Visualization | None | Standard 2D plots, histograms and similarity matrix | None | Standard 2D Plots | Radial plot of neighbors | Interactive neighbor plot | Activity plot | Radial plot of neighborhoods, data matrix, data coverage |
| Output/Export | Output reports in the form of HTML, PDF, or XLSX | SDF or text files of data, image files of plots | Assessment report as DOCX or XLSX, data matrix as XLSX | IUCLID format, PDF and RTF files of prediction report, text files of data, image files of plots | NA | Image files of plots | NA | Output of predictions and associated data from source analogs as represented in the data matrix view as XLSX or CSV |
| Steps covered | Analog identification | All except uncertainty assessment | All except uncertainty assessment | All | All except uncertainty assessment | All except uncertainty assessment | All except uncertainty assessment | All |
a
GenRA was not discussed in Patlewicz et al., 2017 given its release date
b
IUCLID: International Uniform Chemical Information Database; software for the administration of chemical substances data developed to fulfill EU information requirements under REACH