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The application of conformal prediction to the drug discovery process
Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden; AstraZeneca Research and Development, Mölndal, Sweden.
Lundbeck Corporation, Valby, Denmark.
AstraZeneca Research and Development, Mölndal, Sweden.
AstraZeneca Research and Development, Mölndal, Sweden.
2015 (English)In: Annals of Mathematics and Artificial Intelligence, ISSN 1012-2443, E-ISSN 1573-7470, Vol. 74, no 1-2, p. 117-132Article in journal (Refereed) Published
Abstract [en]

QSAR modeling is a method for predicting properties, e.g. the solubility or toxicity, of chemical compounds using machine learning techniques. QSAR is in widespread use within the pharmaceutical industry to prioritize compounds for experimental testing or to alert for potential toxicity during the drug discovery process. However, the confidence or reliability of predictions from a QSAR model are difficult to accurately assess. We frame the application of QSAR to preclinical drug development in an off-line inductive conformal prediction framework and apply it prospectively to historical data collected from four different assays within AstraZeneca over a time course of about five years. The results indicate weakened validity of the conformal predictor due to violations of the randomness assumption. The validity can be strengthen by adopting semi-off-line conformal prediction. The non-randomness of the data prevents exactly valid predictions but comparisons to the results of a traditional QSAR procedure applied to the same data indicate that conformal predictions are highly useful in the drug discovery process.

Place, publisher, year, edition, pages
Springer Science+Business Media B.V., 2015. Vol. 74, no 1-2, p. 117-132
Keywords [en]
QSAR, Conformal prediction, Drug discovery, Temporal model updating
National Category
Pharmaceutical Sciences Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:oru:diva-83154DOI: 10.1007/s10472-013-9378-2ISI: 000355747600007Scopus ID: 2-s2.0-84930414590OAI: oai:DiVA.org:oru-83154DiVA, id: diva2:1440474
Available from: 2015-06-30 Created: 2020-06-15 Last updated: 2020-07-16Bibliographically approved

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Norinder, Ulf

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