Chemical grouping is an important tool that helps researchers and regulators sort through the universe of chemicals to identify the safe, the unsafe, and the useful. The “Chemical Grouping for 21st-Century Toxicology, Risk Assessment, and Decision Making” session during the 2018 Annual Meeting and ToxExpo featured a series of presentations on different ways that grouping chemicals can lead to new insights and more effective chemical selections for a variety of applications and for regulatory purposes. Symposium Chair Jane Simmons, US Environmental Protection Agency (US EPA), indicated the multiple ways that chemicals may be grouped: by structure, function, adverse outcome, physiological target, etc., and remarked that the two most important elements of chemical groupings were 1) a well-defined reason for establishing the group and 2) the criteria used to establish the group. Ensuring transparency on these two points was essential to effective use of chemical groups, she emphasized.
The different presenters focused on chemical grouping in different ways and to different ends. Imran Ali, Karolinska Institutet, presented on the CRAB 3.0 text-mining tool, which enables researchers to identify relevant chemical literature in the PubMed database, simplifying the information collection step of any research project. The software provides metrics on the number and identity of articles that discuss a particular compound and the context in which it is discussed. CRAB’s automated text classification features allow users to organize information about chemicals or groups of chemicals by mode of action and are extraordinarily helpful for distilling the available literature into a manageable format.
While Dr. Ali focused on the literature footprint of individual and groups of chemicals, a presentation from K. De Abrew, Procter and Gamble Company, explored chemicals’ different genomic footprints and demonstrated how connectivity mapping (CMap) could be used to compare biological impacts of chemical exposures across cell lines, doses, and time points. By locating similarities and differences between the genomic footprints, researchers can compare structures and modes of action across chemical groups.
Timothy Allen, University of Cambridge, also investigated the relationships between chemical structures and modes of action. Dr. Allen’s research, however, focused more on the chemicals themselves than the endpoints. The first of his projects examined ways to improve assessment of the minute differences in chemical structure that trigger toxicity alerts in computational models (called structural alerts). He also described efforts to use clever chemical modeling techniques (CoMFA and transition state modeling) to extract additional toxicological and chemical predictions out of in silico models.
The session was rounded out by two US EPA researchers: Mark Nelms and Jeffery Swartout, who explored methods of grouping chemicals at the level of substructure and chemical mixtures, respectively. Dr. Nelms presented on the power of grouping chemicals by structural attribute and his work demonstrated that, depending on how one chops up molecules in the digital realm, one can learn quite a few things about the relationships between structures and functions. Mr. Swartout was more cautious and warned of the challenges and complexities of analyzing mixtures of chemicals and described a number of statistical methods to address these issues.
The ocean of chemicals is large, but finite, and while we may eventually have the time and resources to assess all of them, there’s a lot of work to be done in the immediate future. Grouping chemicals can help researchers use existing data to extract new insights about mechanism and structure-function relationships and to develop new research projects. It takes some finessing to do it well, but when properly executed, chemical grouping can be tremendously valuable.
This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email SOT Communications Director Michelle Werts.