STEP-ping into the World of Computational Toxicology via SOT Funds

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By Niranjana Krishnan posted 12-17-2020 16:20

  

While my PhD dissertation research taught me how to utilize toxicology and exposure information and conduct risk assessments, I did not learn much about computational techniques, which are becoming increasingly important in a Tox21 world. In particular, I was interested in computational toxicology models, like quantitative structure-activity relationship (QSAR) and read-across, that can be used to support risk-based prioritization of chemical inventories and address information gaps in chemical-specific risk assessments. Fortunately, there is a computational toxicology service, ToxNavigation, that provides training in these techniques. With the generous funding through the SOT Supplemental Training for Education Program (STEP), I could attend their live-stream sessions and learn about this exciting field!

ToxNavigation offers a “Use and Applications of QSAR and Read-Across” course that is split into five sessions over five days (12.5 hours total). The course (offered several times in a year) is restricted to five participants to allow for frequent interactions and is taught by Elena Fioravanzo, a computational chemist/toxicologist with over 20 years of experience. Elena did a great job walking us through different concepts, models, and applications, while skillfully answering the many questions I had! Apart from being provided a theoretical understanding, we were also shown how to use several free and commercial software programs and were provided homework questions to allow us to gain a better understanding of the material. At the end of each session, we were provided the presentation slides and video recordings and had the option to attend virtual “office hours” to further discuss topics of interest.

QSAR models and read-across techniques both can predict the biological activity of an untested chemical by using available data from other chemicals. QSAR makes predictions through structural similarities with the help of an algorithm and training set. Read-across is more subjective: the toxicity endpoint (i.e., biological activity) predictions made by a user have to be justified. Both are often used by regulators (for example, scientists in European Chemicals Agency and the US Environmental Protection Agency) to assess and manage chemical risks, by manufacturing companies when developing and registering chemicals, and by pharmaceutical companies during the drug discovery phase.

So, what did the course cover? We started off by looking at chemicals—specifically, their properties, structures, and identifiers—and were introduced to chemical databases like ChemTunes, ChemSpider, CompTox, and COSMOS. We learned how to calculate chemical similarity and molecular descriptors and were instructed on structural alerts (i.e., functional groups that are associated with certain adverse outcomes) and on how to identify them. We were exposed to several QSAR models, like the OECD Toolbox, VEGA, and Danish (Q)SAR Models, and learned to generate QSAR and read-across predictions and assess their reliability. Finally, we were shown ways to deal with uncertainties and report findings. You can get more information about the course on the ToxNavigation website.

One of my goals is to employ computational techniques to my future research and risk assessments, either to lessen the amount of testing needed or to reduce uncertainties in existing data. The Society’s monetary support will certainly go a long way in helping achieve my career goals. I wish the same for other graduate students: please check out the SOT Supplemental Training for Education Program (STEP) and apply. Good luck!


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