A Method for in vitro Data and Structure Curation to Optimize for QSAR Modelling of Minimum Absolute Potency Levels and A Comparative Use Case

Nikolai G. Nikolov; Ana C.V.E. Nissen; Eva B. Wedebye

doi:10.1016/j.etap.2023.104069

A Method for in vitro Data and Structure Curation to Optimize for QSAR Modelling of Minimum Absolute Potency Levels and A Comparative Use Case

Nikolai G. Nikolov, Ana C.V.E. Nissen, Eva B. Wedebye^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

118 Downloads (Pure)

Abstract

Large screening programs such as the US Tox21 are releasing experimental in vitro results for many endpoints of relevance for human health. In (Q)SAR modelling, it is essential to clearly define the endpoint (OECD QSAR Validation Principle 1) and extract the most robust data points according to the definition. We have developed a comprehensive data curation procedure to interpret in vitro experimental data sets for (Q)SAR development, with modules for selecting actives according to quality of curve fittings, magnitude of activity and ‘absolute’ potency cut-offs, requiring non-cytotoxicity at activity concentration; extracting only very robust inactives; selecting only substances tested in high purity; and accounting for assay signal interference. A structure curation procedure with uniform representation of tautomeric classes of substances is also developed. The detailed method and a use case of modelling Tox21 data for an estrogen receptor α agonism assay with and without use of the method is presented.

Original language	English
Article number	104069
Journal	Environmental Toxicology and Pharmacology
Volume	98
Number of pages	15
ISSN	1382-6689
DOIs	https://doi.org/10.1016/j.etap.2023.104069
Publication status	Published - 2023

Bibliographical note

Financial support from the Danish Environmental Protection Agency and the EU Horizon 2020 EURION Cluster projects ATHENA (grant agreement No. 825161) and FREIA (grant agreement No. 825100) is appreciated. We would like also to thank Ruili Huang (US NIH) and Anna K. Rosenmai (DK DTU Food) for discussions of in vitro assays.

Keywords

QSAR
Data curation method
Tox21
Tautomer structure representation
Estrogen receptor
REACH

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.etap.2023.104069Licence: CC BY

FulltextFinal published version, 3.74 MBLicence: CC BY

OpenUrl availability

Full text

Cite this

@article{fc4864a3b85b478db8863a81d092dce1,

title = "A Method for in vitro Data and Structure Curation to Optimize for QSAR Modelling of Minimum Absolute Potency Levels and A Comparative Use Case",

abstract = "Large screening programs such as the US Tox21 are releasing experimental in vitro results for many endpoints of relevance for human health. In (Q)SAR modelling, it is essential to clearly define the endpoint (OECD QSAR Validation Principle 1) and extract the most robust data points according to the definition. We have developed a comprehensive data curation procedure to interpret in vitro experimental data sets for (Q)SAR development, with modules for selecting actives according to quality of curve fittings, magnitude of activity and {\textquoteleft}absolute{\textquoteright} potency cut-offs, requiring non-cytotoxicity at activity concentration; extracting only very robust inactives; selecting only substances tested in high purity; and accounting for assay signal interference. A structure curation procedure with uniform representation of tautomeric classes of substances is also developed. The detailed method and a use case of modelling Tox21 data for an estrogen receptor α agonism assay with and without use of the method is presented.",

keywords = "QSAR, Data curation method, Tox21, Tautomer structure representation, Estrogen receptor, REACH",

author = "Nikolov, {Nikolai G.} and Nissen, {Ana C.V.E.} and Wedebye, {Eva B.}",

note = "Financial support from the Danish Environmental Protection Agency and the EU Horizon 2020 EURION Cluster projects ATHENA (grant agreement No. 825161) and FREIA (grant agreement No. 825100) is appreciated. We would like also to thank Ruili Huang (US NIH) and Anna K. Rosenmai (DK DTU Food) for discussions of in vitro assays.",

year = "2023",

doi = "10.1016/j.etap.2023.104069",

language = "English",

volume = "98",

journal = "Environmental Toxicology and Pharmacology",

issn = "1382-6689",

publisher = "Elsevier",

}

TY - JOUR

T1 - A Method for in vitro Data and Structure Curation to Optimize for QSAR Modelling of Minimum Absolute Potency Levels and A Comparative Use Case

AU - Nikolov, Nikolai G.

AU - Nissen, Ana C.V.E.

AU - Wedebye, Eva B.

N1 - Financial support from the Danish Environmental Protection Agency and the EU Horizon 2020 EURION Cluster projects ATHENA (grant agreement No. 825161) and FREIA (grant agreement No. 825100) is appreciated. We would like also to thank Ruili Huang (US NIH) and Anna K. Rosenmai (DK DTU Food) for discussions of in vitro assays.

PY - 2023

Y1 - 2023

N2 - Large screening programs such as the US Tox21 are releasing experimental in vitro results for many endpoints of relevance for human health. In (Q)SAR modelling, it is essential to clearly define the endpoint (OECD QSAR Validation Principle 1) and extract the most robust data points according to the definition. We have developed a comprehensive data curation procedure to interpret in vitro experimental data sets for (Q)SAR development, with modules for selecting actives according to quality of curve fittings, magnitude of activity and ‘absolute’ potency cut-offs, requiring non-cytotoxicity at activity concentration; extracting only very robust inactives; selecting only substances tested in high purity; and accounting for assay signal interference. A structure curation procedure with uniform representation of tautomeric classes of substances is also developed. The detailed method and a use case of modelling Tox21 data for an estrogen receptor α agonism assay with and without use of the method is presented.

AB - Large screening programs such as the US Tox21 are releasing experimental in vitro results for many endpoints of relevance for human health. In (Q)SAR modelling, it is essential to clearly define the endpoint (OECD QSAR Validation Principle 1) and extract the most robust data points according to the definition. We have developed a comprehensive data curation procedure to interpret in vitro experimental data sets for (Q)SAR development, with modules for selecting actives according to quality of curve fittings, magnitude of activity and ‘absolute’ potency cut-offs, requiring non-cytotoxicity at activity concentration; extracting only very robust inactives; selecting only substances tested in high purity; and accounting for assay signal interference. A structure curation procedure with uniform representation of tautomeric classes of substances is also developed. The detailed method and a use case of modelling Tox21 data for an estrogen receptor α agonism assay with and without use of the method is presented.

KW - QSAR

KW - Data curation method

KW - Tox21

KW - Tautomer structure representation

KW - Estrogen receptor

KW - REACH

U2 - 10.1016/j.etap.2023.104069

DO - 10.1016/j.etap.2023.104069

M3 - Journal article

C2 - 36702390

SN - 1382-6689

VL - 98

JO - Environmental Toxicology and Pharmacology

JF - Environmental Toxicology and Pharmacology

M1 - 104069

ER -

A Method for in vitro Data and Structure Curation to Optimize for QSAR Modelling of Minimum Absolute Potency Levels and A Comparative Use Case

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

OpenUrl availability

Fingerprint

Cite this