Cargando…

Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures

The Toxicology in the 21st Century (Tox21) project seeks to develop and test methods for high-throughput examination of the effect certain chemical compounds have on biological systems. Although primary and toxicity assay data were readily available for multiple reporter gene modified cell lines, ex...

Descripción completa

Detalles Bibliográficos
Autores principales: Cooper, Daniel J., Schürer, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515292/
https://www.ncbi.nlm.nih.gov/pubmed/31018579
http://dx.doi.org/10.3390/molecules24081604
_version_ 1783418058151297024
author Cooper, Daniel J.
Schürer, Stephan
author_facet Cooper, Daniel J.
Schürer, Stephan
author_sort Cooper, Daniel J.
collection PubMed
description The Toxicology in the 21st Century (Tox21) project seeks to develop and test methods for high-throughput examination of the effect certain chemical compounds have on biological systems. Although primary and toxicity assay data were readily available for multiple reporter gene modified cell lines, extensive annotation and curation was required to improve these datasets with respect to how FAIR (Findable, Accessible, Interoperable, and Reusable) they are. In this study, we fully annotated the Tox21 published data with relevant and accepted controlled vocabularies. After removing unreliable data points, we aggregated the results and created three sets of signatures reflecting activity in the reporter gene assays, cytotoxicity, and selective reporter gene activity, respectively. We benchmarked these signatures using the chemical structures of the tested compounds and obtained generally high receiver operating characteristic (ROC) scores, suggesting good quality and utility of these signatures and the underlying data. We analyzed the results to identify promiscuous individual compounds and chemotypes for the three signature categories and interpreted the results to illustrate the utility and re-usability of the datasets. With this study, we aimed to demonstrate the importance of data standards in reporting screening results and high-quality annotations to enable re-use and interpretation of these data. To improve the data with respect to all FAIR criteria, all assay annotations, cleaned and aggregate datasets, and signatures were made available as standardized dataset packages (Aggregated Tox21 bioactivity data, 2019).
format Online
Article
Text
id pubmed-6515292
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65152922019-05-30 Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures Cooper, Daniel J. Schürer, Stephan Molecules Article The Toxicology in the 21st Century (Tox21) project seeks to develop and test methods for high-throughput examination of the effect certain chemical compounds have on biological systems. Although primary and toxicity assay data were readily available for multiple reporter gene modified cell lines, extensive annotation and curation was required to improve these datasets with respect to how FAIR (Findable, Accessible, Interoperable, and Reusable) they are. In this study, we fully annotated the Tox21 published data with relevant and accepted controlled vocabularies. After removing unreliable data points, we aggregated the results and created three sets of signatures reflecting activity in the reporter gene assays, cytotoxicity, and selective reporter gene activity, respectively. We benchmarked these signatures using the chemical structures of the tested compounds and obtained generally high receiver operating characteristic (ROC) scores, suggesting good quality and utility of these signatures and the underlying data. We analyzed the results to identify promiscuous individual compounds and chemotypes for the three signature categories and interpreted the results to illustrate the utility and re-usability of the datasets. With this study, we aimed to demonstrate the importance of data standards in reporting screening results and high-quality annotations to enable re-use and interpretation of these data. To improve the data with respect to all FAIR criteria, all assay annotations, cleaned and aggregate datasets, and signatures were made available as standardized dataset packages (Aggregated Tox21 bioactivity data, 2019). MDPI 2019-04-23 /pmc/articles/PMC6515292/ /pubmed/31018579 http://dx.doi.org/10.3390/molecules24081604 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cooper, Daniel J.
Schürer, Stephan
Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
title Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
title_full Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
title_fullStr Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
title_full_unstemmed Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
title_short Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
title_sort improving the utility of the tox21 dataset by deep metadata annotations and constructing reusable benchmarked chemical reference signatures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515292/
https://www.ncbi.nlm.nih.gov/pubmed/31018579
http://dx.doi.org/10.3390/molecules24081604
work_keys_str_mv AT cooperdanielj improvingtheutilityofthetox21datasetbydeepmetadataannotationsandconstructingreusablebenchmarkedchemicalreferencesignatures
AT schurerstephan improvingtheutilityofthetox21datasetbydeepmetadataannotationsandconstructingreusablebenchmarkedchemicalreferencesignatures