Toxicology Domain Research Articles

Mechanistic Task Groupings Enhance Multitask Deep Learning of Strain-Specific Ames Mutagenicity.

The Ames test is a gold standard mutagenicity assay that utilizes various Salmonella typhimurium strains with and without S9 fraction to provide insights into the mechanisms by which a chemical can mutate DNA. Multitask deep learning is an ideal framework for developing QSAR models with multiple end points, such as the Ames test, as the joint training of multiple predictive tasks may synergistically improve the prediction accuracy of each task. This work investigated how toxicology domain knowledge can be used to handcraft task groupings that better guide the training of multitask neural networks compared to a naïve ungrouped multitask neural network developed on a complete set of tasks. Sixteen S. typhimurium ± S9 strain tasks were used to generate groupings based on mutagenic and metabolic mechanisms that were reflected in correlation data analyses. Both grouped and ungrouped multitask neural networks predicted the 16 strain tasks with a higher balanced accuracy compared with single task controls, with grouped multitask neural networks consistently featuring incremental increases in predictivity over the ungrouped approach. We conclude that the main variable driving these performance improvements is the general multitask effect with mechanistic task groupings acting as an enhancement step to further concentrate synergistic training signals united by a common biological mechanism. This approach enables incorporation of toxicology domain knowledge into multitask QSAR model development allowing for more transparent and accurate Ames mutagenicity prediction.

Concept drift detection in toxicology datasets using discriminative subgraph-based drift detector.

Due to the increasing importance of graphs and graph streams in data representation in today's era, concept drift detection in graph streaming scenarios is more important than ever. Contributions to concept drift detection in graph streams are minimal and practically non-existent in the field of toxicology. This paper applied the discriminative subgraph-based drift detector (DSDD) to graph streams generated from real-world toxicology datasets. We used four toxicology datasets, each of which yielded two graph streams - one with abrupt drift points and one with gradual drift points. We used DSDD both with the standard minimum description length (MDL) heuristic and after replacing MDL with a much simpler heuristic SIZE (number of vertices + number of edges), and applied it to all generated graph streams containing abrupt drift points and gradual drift points for varying window sizes. Following that, we compared and analyzed the results. Finally, we applied a long short-term memory based graph stream classification model to all the generated streams and compared the difference in the performances obtained with and without detecting drift using DSDD. We believe that the results and analysis presented in this paper will provide insight into the task of concept drift detection in the toxicology domain and aid in the application of DSDD in a variety of scenarios.

End-user engineering of ontology-based knowledge bases

ABSTRACT Knowledge bases store information on certain topics. Applying a well-structured and machine-readable format for a knowledge base is a prerequisite for any AI-based processing or reasoning. Semantic technologies (e.g. RDF) offer such a format and have the advantages that they make it possible to define the semantics of the information and support advanced querying. However, the disadvantage is that using such technologies is challenging for people not trained in IT, such as subject matter experts. This means that they need to rely on semantic technology experts to create, maintain, and query their knowledge bases. However, these experts are, in turn, not trained in the subject matter, while domain knowledge is essential for the construction of high-quality knowledge bases. In this paper, we present an end-user engineering approach for ontology-based knowledge bases. The goal is to allow subject matter experts to develop, maintain, and exploit the knowledge base themselves. We also present the supporting tools developed so far. The tools for the construction and the manual filling of the knowledge base are using the jigsaw metaphor to hide technicalities and guide the users. We also developed tools to automatically import data from spreadsheets into the knowledge base and to perform some type of quality control on the data. The end-user approach and the tools are demonstrated and evaluated for building a knowledge base in the toxicology domain.

Should We Embed in Chemistry? A Comparison of Unsupervised Transfer Learning with PCA, UMAP, and VAE on Molecular Fingerprints.

Methods for dimensionality reduction are showing significant contributions to knowledge generation in high-dimensional modeling scenarios throughout many disciplines. By achieving a lower dimensional representation (also called embedding), fewer computing resources are needed in downstream machine learning tasks, thus leading to a faster training time, lower complexity, and statistical flexibility. In this work, we investigate the utility of three prominent unsupervised embedding techniques (principal component analysis—PCA, uniform manifold approximation and projection—UMAP, and variational autoencoders—VAEs) for solving classification tasks in the domain of toxicology. To this end, we compare these embedding techniques against a set of molecular fingerprint-based models that do not utilize additional pre-preprocessing of features. Inspired by the success of transfer learning in several fields, we further study the performance of embedders when trained on an external dataset of chemical compounds. To gain a better understanding of their characteristics, we evaluate the embedders with different embedding dimensionalities, and with different sizes of the external dataset. Our findings show that the recently popularized UMAP approach can be utilized alongside known techniques such as PCA and VAE as a pre-compression technique in the toxicology domain. Nevertheless, the generative model of VAE shows an advantage in pre-compressing the data with respect to classification accuracy.