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Skin Doctor CP :
Skin Doctor CP : Conformal Prediction of the Skin Sensitization Potential of Small Organic Molecules
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- Wilm, Anke (author)
- Center for Bioinformatics (ZBH), Department of Informatics, Universität Hamburg, Hamburg, Germany; HITeC e.V., Hamburg, Germany,Univ Hamburg, Ctr Bioinformat ZBH, Dept Informat, D-20146 Hamburg, Germany.;HITeC eV, D-22527 Hamburg, Germany.
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- Norinder, Ulf, 1956- (author)
- Uppsala universitet,Stockholms universitet,Örebro universitet,Institutionen för naturvetenskap och teknik,Department of Computer and Systems Sciences, Stockholm University, Kista, Sweden; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden,MTM Research Centre, School of Science and Technology,Institutionen för data- och systemvetenskap,Uppsala University, Sweden; Örebro University, Sweden,Institutionen för farmaceutisk biovetenskap,Stockholm Univ, Dept Comp & Syst Sci, SE-16407 Kista, Sweden.;Örebro Univ, MTM Res Ctr, Sch Sci & Technol, SE-70182 Örebro, Sweden.
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- Agea, M. Isabel (author)
- Department of Informatics and Chemistry, University of Chemistry and Technology Prague, Prague, Czech Republic,Univ Chem & Technol Prague, Dept Informat & Chem, Prague 16628, Czech Republic.
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- de Bruyn Kops, Christina (author)
- Center for Bioinformatics (ZBH), Department of Informatics, Universität Hamburg, Hamburg, Germany,Univ Hamburg, Ctr Bioinformat ZBH, Dept Informat, D-20146 Hamburg, Germany.
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- Stork, Conrad (author)
- Center for Bioinformatics (ZBH), Department of Informatics, Universität Hamburg, Hamburg, Germany,Univ Hamburg, Ctr Bioinformat ZBH, Dept Informat, D-20146 Hamburg, Germany.
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- Kühnl, Jochen (author)
- Front End Innovation, Beiersdorf AG, Hamburg, Germany,Beiersdorf AG, Front End Innovat, D-22529 Hamburg, Germany.
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- Kirchmair, Johannes (author)
- Center for Bioinformatics (ZBH), Department of Informatics, Universität Hamburg, Hamburg, Germany; Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria,Univ Hamburg, Ctr Bioinformat ZBH, Dept Informat, D-20146 Hamburg, Germany.;Univ Vienna, Dept Pharmaceut Chem, A-1090 Vienna, Austria.
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Center for Bioinformatics (ZBH), Department of Informatics, Universität Hamburg, Hamburg, Germany; HITeC eV., Hamburg, Germany Univ Hamburg, Ctr Bioinformat ZBH, Dept Informat, D-20146 Hamburg, Germany.;HITeC eV, D-22527 Hamburg, Germany. (creator_code:org_t)
- 2020-12-09
- 2021
- English.
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In: Chemical Research in Toxicology. - : ACS Publications. - 0893-228X .- 1520-5010. ; 34:2, s. 330-344
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Abstract
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- Skin sensitization potential or potency is an important end point in the safety assessment of new chemicals and new chemical mixtures. Formerly, animal experiments such as the local lymph node assay (LLNA) were the main form of assessment. Today, however, the focus lies on the development of nonanimal testing approaches (i.e., in vitro and in chemico assays) and computational models. In this work, we investigate, based on publicly available LLNA data, the ability of aggregated, Mondrian conformal prediction classifiers to differentiate between non- sensitizing and sensitizing compounds as well as between two levels of skin sensitization potential (weak to moderate sensitizers, and strong to extreme sensitizers). The advantage of the conformal prediction framework over other modeling approaches is that it assigns compounds to activity classes only if a defined minimum level of confidence is reached for the individual predictions. This eliminates the need for applicability domain criteria that often are arbitrary in their nature and less flexible. Our new binary classifier, named Skin Doctor CP, differentiates nonsensitizers from sensitizers with a higher reliability-to-efficiency ratio than the corresponding nonconformal prediction workflow that we presented earlier. When tested on a set of 257 compounds at the significance levels of 0.10 and 0.30, the model reached an efficiency of 0.49 and 0.92, and an accuracy of 0.83 and 0.75, respectively. In addition, we developed a ternary classification workflow to differentiate nonsensitizers, weak to moderate sensitizers, and strong to extreme sensitizers. Although this model achieved satisfactory overall performance (accuracies of 0.90 and 0.73, and efficiencies of 0.42 and 0.90, at significance levels 0.10 and 0.30, respectively), it did not obtain satisfying class-wise results (at a significance level of 0.30, the validities obtained for nonsensitizers, weak to moderate sensitizers, and strong to extreme sensitizers were 0.70, 0.58, and 0.63, respectively). We argue that the model is, in consequence, unable to reliably identify strong to extreme sensitizers and suggest that other ternary models derived from the currently accessible LLNA data might suffer from the same problem. Skin Doctor CP is available via a public web service at https://nerdd.zbh.uni-hamburg.de/skinDoctorII/.
Subject headings
- NATURVETENSKAP -- Data- och informationsvetenskap -- Bioinformatik (hsv//swe)
- NATURAL SCIENCES -- Computer and Information Sciences -- Bioinformatics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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