@article{davis_wiegers_sciaky_barkalow_strong_wyatt_wiegers_mcmorran_abrar_mattingly_2024, title={Comparative toxicogenomics database's 20th anniversary: update 2025}, volume={10}, ISSN={["1362-4962"]}, DOI={10.1093/nar/gkae883}, abstractNote={For 20 years, the Comparative Toxicogenomics Database (CTD; https://ctdbase.org) has provided high-quality, literature-based curated content describing how environmental chemicals affect human health. Today, CTD includes over 94 million toxicogenomic connections relating chemicals, genes/proteins, phenotypes, anatomical terms, diseases, comparative species, pathways and exposures. In this 20th year anniversary update, we reflect on CTD's remarkable growth and provide an overview of the increased data content and new features, including enhancements to the curation workflow (e.g. new exposure curation tool and expanded use of natural language processing), added functionality (e.g. improvements to CTD Tetramers and Pathway View tools) and significant upgrades to software and infrastructure. Linking lab-based core curation with real-world human exposure curation via the use of controlled vocabularies facilitates analysis of content across the entire environmental health continuum, from molecular toxicological mechanisms to the population level, and vice versa. The 'prototype database' originally described in 2004 has evolved into a premier, sophisticated, highly cited and well-engineered knowledgebase and discoverybase that is utilized by scientists worldwide to design testable hypotheses about environmental health.}, journal={NUCLEIC ACIDS RESEARCH}, author={Davis, Allan Peter and Wiegers, Thomas C. and Sciaky, Daniela and Barkalow, Fern and Strong, Melissa and Wyatt, Brent and Wiegers, Jolene and McMorran, Roy and Abrar, Sakib and Mattingly, Carolyn J.}, year={2024}, month={Oct} }
 @article{wyatt_davis_wiegers_wiegers_abrar_sciaky_barkalow_strong_mattingly_2024, title={Transforming environmental health datasets from the comparative toxicogenomics database into chord diagrams to visualize molecular mechanisms}, volume={6}, ISSN={["2673-3080"]}, DOI={10.3389/ftox.2024.1437884}, abstractNote={In environmental health, the specific molecular mechanisms connecting a chemical exposure to an adverse endpoint are often unknown, reflecting knowledge gaps. At the public Comparative Toxicogenomics Database (CTD; https://ctdbase.org/), we integrate manually curated, literature-based interactions from CTD to compute four-unit blocks of information organized as a potential step-wise molecular mechanism, known as "CGPD-tetramers," wherein a chemical interacts with a gene product to trigger a phenotype which can be linked to a disease. These computationally derived datasets can be used to fill the gaps and offer testable mechanistic information. Users can generate CGPD-tetramers for any combination of chemical, gene, phenotype, and/or disease of interest at CTD; however, such queries typically result in the generation of thousands of CGPD-tetramers. Here, we describe a novel approach to transform these large datasets into user-friendly chord diagrams using R. This visualization process is straightforward, simple to implement, and accessible to inexperienced users that have never used R before. Combining CGPD-tetramers into a single chord diagram helps identify potential key chemicals, genes, phenotypes, and diseases. This visualization allows users to more readily analyze computational datasets that can fill the exposure knowledge gaps in the environmental health continuum.}, journal={FRONTIERS IN TOXICOLOGY}, author={Wyatt, Brent and Davis, Allan Peter and Wiegers, Thomas C. and Wiegers, Jolene and Abrar, Sakib and Sciaky, Daniela and Barkalow, Fern and Strong, Melissa and Mattingly, Carolyn J.}, year={2024}, month={Jul} }
 @article{davis_wiegers_wiegers_wyatt_johnson_sciaky_barkalow_strong_planchart_mattingly_2023, title={CTD tetramers: a new online tool that computationally links curated chemicals, genes, phenotypes, and diseases to inform molecular mechanisms for environmental health}, volume={195}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfad069}, abstractNote={Abstract
               The molecular mechanisms connecting environmental exposures to adverse endpoints are often unknown, reflecting knowledge gaps. At the Comparative Toxicogenomics Database (CTD), we developed a bioinformatics approach that integrates manually curated, literature-based interactions from CTD to generate a “CGPD-tetramer”: a 4-unit block of information organized as a step-wise molecular mechanism linking an initiating Chemical, an interacting Gene, a Phenotype, and a Disease outcome. Here, we describe a novel, user-friendly tool called CTD Tetramers that generates these evidence-based CGPD-tetramers for any curated chemical, gene, phenotype, or disease of interest. Tetramers offer potential solutions for the unknown underlying mechanisms and intermediary phenotypes connecting a chemical exposure to a disease. Additionally, multiple tetramers can be assembled to construct detailed modes-of-action for chemical-induced disease pathways. As well, tetramers can help inform environmental influences on adverse outcome pathways (AOPs). We demonstrate the tool’s utility with relevant use cases for a variety of environmental chemicals (eg, perfluoroalkyl substances, bisphenol A), phenotypes (eg, apoptosis, spermatogenesis, inflammatory response), and diseases (eg, asthma, obesity, male infertility). Finally, we map AOP adverse outcome terms to corresponding CTD terms, allowing users to query for tetramers that can help augment AOP pathways with additional stressors, genes, and phenotypes, as well as formulate potential AOP disease networks (eg, liver cirrhosis and prostate cancer). This novel tool, as part of the complete suite of tools offered at CTD, provides users with computational datasets and their supporting evidence to potentially fill exposure knowledge gaps and develop testable hypotheses about environmental health.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Davis, Allan Peter and Wiegers, Thomas C. and Wiegers, Jolene and Wyatt, Brent and Johnson, Robin J. and Sciaky, Daniela and Barkalow, Fern and Strong, Melissa and Planchart, Antonio and Mattingly, Carolyn J.}, year={2023}, month={Sep}, pages={155–168} }