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The ToxCast pipeline: updates to curve-fitting approaches and database structure

Introduction: The US Environmental Protection Agency Toxicity Forecaster (ToxCast) program makes in vitro medium- and high-throughput screening assay data publicly available for prioritization and hazard characterization of thousands of chemicals. The assays employ a variety of technologies to evalu...

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Autores principales: Feshuk, M., Kolaczkowski, L., Dunham, K., Davidson-Fritz, S. E., Carstens, K. E., Brown, J., Judson, R. S., Paul Friedman, K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552852/
https://www.ncbi.nlm.nih.gov/pubmed/37808181
http://dx.doi.org/10.3389/ftox.2023.1275980
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author Feshuk, M.
Kolaczkowski, L.
Dunham, K.
Davidson-Fritz, S. E.
Carstens, K. E.
Brown, J.
Judson, R. S.
Paul Friedman, K.
author_facet Feshuk, M.
Kolaczkowski, L.
Dunham, K.
Davidson-Fritz, S. E.
Carstens, K. E.
Brown, J.
Judson, R. S.
Paul Friedman, K.
author_sort Feshuk, M.
collection PubMed
description Introduction: The US Environmental Protection Agency Toxicity Forecaster (ToxCast) program makes in vitro medium- and high-throughput screening assay data publicly available for prioritization and hazard characterization of thousands of chemicals. The assays employ a variety of technologies to evaluate the effects of chemical exposure on diverse biological targets, from distinct proteins to more complex cellular processes like mitochondrial toxicity, nuclear receptor signaling, immune responses, and developmental toxicity. The ToxCast data pipeline (tcpl) is an open-source R package that stores, manages, curve-fits, and visualizes ToxCast data and populates the linked MySQL Database, invitrodb. Methods: Herein we describe major updates to tcpl and invitrodb to accommodate a new curve-fitting approach. The original tcpl curve-fitting models (constant, Hill, and gain-loss models) have been expanded to include Polynomial 1 (Linear), Polynomial 2 (Quadratic), Power, Exponential 2, Exponential 3, Exponential 4, and Exponential 5 based on BMDExpress and encoded by the R package dependency, tcplfit2. Inclusion of these models impacted invitrodb (beta version v4.0) and tcpl v3 in several ways: (1) long-format storage of generic modeling parameters to permit additional curve-fitting models; (2) updated logic for winning model selection; (3) continuous hit calling logic; and (4) removal of redundant endpoints as a result of bidirectional fitting. Results and discussion: Overall, the hit call and potency estimates were largely consistent between invitrodb v3.5 and 4.0. Tcpl and invitrodb provide a standard for consistent and reproducible curve-fitting and data management for diverse, targeted in vitro assay data with readily available documentation, thus enabling sharing and use of these data in myriad toxicology applications. The software and database updates described herein promote comparability across multiple tiers of data within the US Environmental Protection Agency CompTox Blueprint.
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spelling pubmed-105528522023-10-06 The ToxCast pipeline: updates to curve-fitting approaches and database structure Feshuk, M. Kolaczkowski, L. Dunham, K. Davidson-Fritz, S. E. Carstens, K. E. Brown, J. Judson, R. S. Paul Friedman, K. Front Toxicol Toxicology Introduction: The US Environmental Protection Agency Toxicity Forecaster (ToxCast) program makes in vitro medium- and high-throughput screening assay data publicly available for prioritization and hazard characterization of thousands of chemicals. The assays employ a variety of technologies to evaluate the effects of chemical exposure on diverse biological targets, from distinct proteins to more complex cellular processes like mitochondrial toxicity, nuclear receptor signaling, immune responses, and developmental toxicity. The ToxCast data pipeline (tcpl) is an open-source R package that stores, manages, curve-fits, and visualizes ToxCast data and populates the linked MySQL Database, invitrodb. Methods: Herein we describe major updates to tcpl and invitrodb to accommodate a new curve-fitting approach. The original tcpl curve-fitting models (constant, Hill, and gain-loss models) have been expanded to include Polynomial 1 (Linear), Polynomial 2 (Quadratic), Power, Exponential 2, Exponential 3, Exponential 4, and Exponential 5 based on BMDExpress and encoded by the R package dependency, tcplfit2. Inclusion of these models impacted invitrodb (beta version v4.0) and tcpl v3 in several ways: (1) long-format storage of generic modeling parameters to permit additional curve-fitting models; (2) updated logic for winning model selection; (3) continuous hit calling logic; and (4) removal of redundant endpoints as a result of bidirectional fitting. Results and discussion: Overall, the hit call and potency estimates were largely consistent between invitrodb v3.5 and 4.0. Tcpl and invitrodb provide a standard for consistent and reproducible curve-fitting and data management for diverse, targeted in vitro assay data with readily available documentation, thus enabling sharing and use of these data in myriad toxicology applications. The software and database updates described herein promote comparability across multiple tiers of data within the US Environmental Protection Agency CompTox Blueprint. Frontiers Media S.A. 2023-09-21 /pmc/articles/PMC10552852/ /pubmed/37808181 http://dx.doi.org/10.3389/ftox.2023.1275980 Text en Copyright © 2023 Feshuk, Kolaczkowski, Dunham, Davidson-Fritz, Carstens, Brown, Judson and Paul Friedman. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Toxicology
Feshuk, M.
Kolaczkowski, L.
Dunham, K.
Davidson-Fritz, S. E.
Carstens, K. E.
Brown, J.
Judson, R. S.
Paul Friedman, K.
The ToxCast pipeline: updates to curve-fitting approaches and database structure
title The ToxCast pipeline: updates to curve-fitting approaches and database structure
title_full The ToxCast pipeline: updates to curve-fitting approaches and database structure
title_fullStr The ToxCast pipeline: updates to curve-fitting approaches and database structure
title_full_unstemmed The ToxCast pipeline: updates to curve-fitting approaches and database structure
title_short The ToxCast pipeline: updates to curve-fitting approaches and database structure
title_sort toxcast pipeline: updates to curve-fitting approaches and database structure
topic Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552852/
https://www.ncbi.nlm.nih.gov/pubmed/37808181
http://dx.doi.org/10.3389/ftox.2023.1275980
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