• COSMOS next generation - A public knowledge base leveraging chemical and biological data to support the regulatory assessment of chemicals

      Yang, C.; Cronin, M.T.D.; Arvidson, K.B.; Bienfait, B.; Enoch, S.J.; Heldreth, B.; Hobocienski, B.; Muldoon-Jacobs, K.; Lan, Y.; Madden, J.C.; et al. (2021-08)
      The COSMOS Database (DB) was originally established to provide reliable data for cosmetics-related chemicals within the COSMOS Project funded as part of the SEURAT-1 Research Initiative. The database has subsequently been maintained and developed further into COSMOS Next Generation (NG), a combination of database and in silico tools, essential components of a knowledge base. COSMOS DB provided a cosmetics inventory as well as other regulatory inventories, accompanied by assessment results and in vitro and in vivo toxicity data. In addition to data content curation, much effort was dedicated to data governance - data authorisation, characterisation of quality, documentation of meta information, and control of data use. Through this effort, COSMOS DB was able to merge and fuse data of various types from different sources. Building on the previous effort, the COSMOS Minimum Inclusion (MINIS) criteria for a toxicity database were further expanded to quantify the reliability of studies. COSMOS NG features multiple fingerprints for analysing structure similarity, and new tools to calculate molecular properties and screen chemicals with endpoint-related public profilers, such as DNA and protein binders, liver alerts and genotoxic alerts. The publicly available COSMOS NG enables users to compile information and execute analyses such as category formation and read-across. This paper provides a step-by-step guided workflow for a simple read-across case, starting from a target structure and culminating in an estimation of a NOAEL confidence interval. Given its strong technical foundation, inclusion of quality-reviewed data, and provision of tools designed to facilitate communication between users, COSMOS NG is a first step towards building a toxicological knowledge hub leveraging many public data systems for chemical safety evaluation. We continue to monitor the feedback from the user community at support@mn-am.com.
    • Towards a Fuzzy Expert System on Toxicological Data Quality Assessment

      Yang, Longzhi; Neagu, Daniel; Cronin, M.T.D.; Hewitt, M.; Enoch, S.J.; Madden, J.C.; Przybylak, K. (2013-01)
      Quality assessment (QA) requires high levels of domain-specific experience and knowledge. QA tasks for toxicological data are usually performed by human experts manually, although a number of quality evaluation schemes have been proposed in the literature. For instance, the most widely utilised Klimisch scheme1 defines four data quality categories in order to tag data instances with respect to their qualities; ToxRTool2 is an extension of the Klimisch approach aiming to increase the transparency and harmonisation of the approach. Note that the processes of QA in many other areas have been automatised by employing expert systems. Briefly, an expert system is a computer program that uses a knowledge base built upon human expertise, and an inference engine that mimics the reasoning processes of human experts to infer new statements from incoming data. In particular, expert systems have been extended to deal with the uncertainty of information by representing uncertain information (such as linguistic terms) as fuzzy sets under the framework of fuzzy set theory and performing inferences upon fuzzy sets according to fuzzy arithmetic. This paper presents an experimental fuzzy expert system for toxicological data QA which is developed on the basis of the Klimisch approach and the ToxRTool in an effort to illustrate the power of expert systems to toxicologists, and to examine if fuzzy expert systems are a viable solution for QA of toxicological data. Such direction still faces great difficulties due to the well-known common challenge of toxicological data QA that "five toxicologists may have six opinions". In the meantime, this challenge may offer an opportunity for expert systems because the construction and refinement of the knowledge base could be a converging process of different opinions which is of significant importance for regulatory policy making under the regulation of REACH, though a consensus may never be reached. Also, in order to facilitate the implementation of Weight of Evidence approaches and in silico modelling proposed by REACH, there is a higher appeal of numerical quality values than nominal (categorical) ones, where the proposed fuzzy expert system could help. Most importantly, the deriving processes of quality values generated in this way are fully transparent, and thus comprehensible, for final users, which is another vital point for policy making specified in REACH. Case studies have been conducted and this report not only shows the promise of the approach, but also demonstrates the difficulties of the approach and thus indicates areas for future development.