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Laying the foundation for bioinformatics in cross-species extrapolation of chemical toxicity information: Hands-on experience with the SeqAPASS tool
Citation:
LaLone, C., S. Mayasich, M. Jensen, AND D. Blatz. Laying the foundation for bioinformatics in cross-species extrapolation of chemical toxicity information: Hands-on experience with the SeqAPASS tool. SETAC North America 42nd Annual meeting November 2021, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.21266217
Impact/Purpose:
Short course presented to the SETAC North America 42nd Annual meeting November 2021. The aims of the short course are to 1) generate awareness of ongoing challenges related to species extrapolation in toxicology and regulatory decision-making; and 2) demonstrate the utility of a new tool, Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) for addressing these challenges. A component of the course will describe the methodology behind the SeqAPASS tool and best practices for use in cross-species extrapolation. The course will provide the participants with the theory and hands-on skills that will facilitate independent use of the SeqAPASS tool (https://seqapass.epa.gov/seqapass/). Specific objectives of session: • Introduce participants to known challenges and questions that arise in research and regulatory decision making relative to species extrapolation. • Familiarize participants with current tools available for species extrapolation. • Provide participants with an understanding of the scientific underpinnings, strengths, and limitations of the SeqAPASS tool and methodology. • Provide participants with hands-on experience in querying and navigating the SeqAPASS tool. • Provide participants with hands-on experience developing a line of evidence to supporting extrapolation of toxicity data/pathway knowledge across species. • Discuss the domain of applicability for SeqAPASS cross-species chemical susceptibility predictions.
Description:
It is recognized that limited empirical data is available for a majority of chemicals in commerce for the evaluation of chemical toxicity. Further, data describing the potential adverse effects of chemicals across species is even more sparse. Therefore, novel strategies are needed to make the greatest use of existing data to understand chemical effects across species. Aligning with the vision and strategy for toxicity testing in the 21st century, in silico approaches to species extrapolation are being explored to address the question of how broadly toxicity data and pathway knowledge can be extrapolated across taxa. An underutilized data source for purposes of species extrapolation is protein sequence and structural information. With sequencing and annotation techniques becoming more cost-effective and streamlined, this growing source of data served as the motivation for developing the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool, that utilizes this data to predict chemical susceptibility across species based on concepts derived from evolutionary biology. The assumption underlying the SeqAPASS tool is that the greater the similarity between the protein target in a sensitive or model organism to other species, the more likely the protein in the other species functions similarly, either binding to a chemical or performing a similar role in a pathway. This knowledge of conservation across species from SeqAPASS provides a rapid mechanism for understanding how well model organisms serve as surrogates for other untested species and provides a line of evidence for extrapolation of toxicity or pathway data to other species based on chemical molecular target conservation. Topics: The course will cover: • Challenges in species extrapolation; Introduction to the computational tools, with a focus on SeqAPASS - what is it, how has it been applied for species extrapolation? • Requesting a SeqAPASS Account • SeqAPASS Demonstration • Case examples for users to work through • Data visualization • Decision Summary Report • Advances in Bioinformatics • Integration of Bioinformatics in decision-making
URLs/Downloads:
DOI: Laying the foundation for bioinformatics in cross-species extrapolation of chemical toxicity information: Hands-on experience with the SeqAPASS tool
SETAC_PORTLAND_SEQAPASS_INTRO_TRAINING_CL.PDF (PDF, NA pp, 7405.49 KB, about PDF)
SETAC_PORTLAND_SEQAPASS_LEVEL 3_TRAINING_MJ.PDF (PDF, NA pp, 1248.509 KB, about PDF)
SETAC_PORTLAND_SEQAPASS_INTEROPERABILITY_TRAINING_CL.PDF (PDF, NA pp, 1631.814 KB, about PDF)
SETAC_PORTLAND_SEQAPASS_LEVEL 1_TRAINING_SMR1.PDF (PDF, NA pp, 1109.774 KB, about PDF)
SETAC_PORTLAND_SEQAPASS_DECISION SUMMARY REPORT_TRAINING_DB.PDF (PDF, NA pp, 2037.144 KB, about PDF)
SETAC_PORTLAND_SEQAPASS_WHATSNEXT_SM.PDF (PDF, NA pp, 1308.638 KB, about PDF)
SETAC_PORTLAND_SEQAPASS_LEVEL 2_TRAINING_CL.PDF (PDF, NA pp, 1369.566 KB, about PDF)