ICE: Integrated Chemical Environment
A training event held in April 2022 featured NICEATM developers demonstrating how to use ICE tools for data and assay exploration. These tools provide access to data adhering to FAIR principles-—Findable, Accessible, Interoperable, and Reusable—for analyses including in vitro to in vivo extrapolation and physiologically based pharmacokinetic modeling. The training was organized by PCRM, and the videos are available on their website.
Successful computational toxicology projects depend on high-quality data that are freely available and formatted for use in computational workflows. The Integrated Chemical Environment (ICE) addresses the data needs frequently expressed by NICEATM stakeholders. Launched in March 2017, ICE provides curated data from NICEATM, its partners, and other resources, as well as tools to facilitate the safety assessment of chemicals.
The ICE Chemical Quest tool was released in June 2021 with ICE version 3.4. Chemical Quest uses Saagar fingerprints (Sedykh et al. 2021) to predict structure similarity, allowing users to query the ICE database for chemicals similar to a chemical of interest. Chemical Quest includes a drawing tool that allows users to draw their own structures and query ICE for all chemicals that are similar to the drawn structure.
The March 2022 ICE 3.6 update added new result filtering options to Chemical Quest and the ICE Curve Surfer tool; the ability to limit Chemical Quest searches to chemicals in user-defined lists; new viewing options in Curve Surfer; an updated view to upload custom in vivo and in vitro data to the IVIVE tool; and updated cHTS, acute oral toxicity, skin sensitization, and endocrine data.
The July 2022 ICE 3.7 update implemented REST APIs to allow users to access ICE data more easily via database searches outside of the ICE environment. The 3.7 update also improved the user interface and supporting documentation, provided help videos for the PBPK and Curve Surfer tools, and added a Publications section with pages listing journal articles, oral presentations, and poster presentations about ICE. Further updates in October 2022 added new and updated predictions from the latest version of the Open (Quantitative) Structure-activity/property Relationship App (OPERA) and improvements in the Saagar fingerprints.
Other recent improvements to ICE include:
- Support for inputs of multiple chemical identifiers: CASRNs, DTXSIDs, SMILES, or InChIKeys.
- Ability to send assays selected in one ICE tool to query other ICE tools.
- Detailed visualizations of ICE Search results.
- New visualizations of query results from the ICE Chemical Characterization tool, including bioactivity PCA plots and the Consumer Use Explorer, which allows users to view chemical use categories from the EPA Consumer Products Database (CPDat).
An article in the November 2021 issue of Computational Toxicology (Abedini et al. 2021) provides the most recent detailed overview of ICE.
ICE includes data from animal and non-animal tests that measure toxic effects described in chemical safety regulations. These effects include acute oral toxicity, skin and eye irritation, skin sensitization, and endocrine activity. The ICE Search tool enables users to easily query and integrate data streams and explore the results interactively. ICE also contains curated HTS data from the Tox21 consortium and physicochemical property data about chemicals including solubility, melting point, and molecular weight.
NICEATM curation of Tox21 data minimizes low-confidence hit calls, providing a processed version of the HTS data that is ready for any application. Factors considered in the curation include chemical purity, quality control data, concentration-response curve fits, and testing range. To facilitate targeted access of Tox21 data by ICE tools, NICEATM also maps HTS assay endpoints to adverse toxicological outcomes such as developmental toxicity, acute toxicity, and carcinogenicity based on established modes of action from literature.