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Predicting With Confidence: Using Conformal Prediction in Drug Discovery
Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences. Uppsala University, Sweden; Örebro University, Sweden.
Number of Authors: 42021 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 110, no 1, p. 42-49Article, review/survey (Refereed) Published
Abstract [en]

One of the challenges with predictive modeling is how to quantify the reliability of the models' predictions on new objects. In this work we give an introduction to conformal prediction, a framework that sits on top of traditional machine learning algorithms and which outputs valid confidence estimates to predictions from QSAR models in the form of prediction intervals that are specific to each predicted object. For regression, a prediction interval consists of an upper and a lower bound. For classification, a prediction interval is a set that contains none, one, or many of the potential classes. The size of the prediction interval is affected by a user-specified confidence/significance level, and by the nonconformity of the predicted object; i.e., the strangeness as defined by a nonconformity function. Conformal prediction provides a rigorous and mathematically proven framework for in silico modeling with guarantees on error rates as well as a consistent handling of the models' applicability domain intrinsically linked to the underlying machine learning model. Apart from introducing the concepts and types of conformal prediction, we also provide an example application for modeling ABC transporters using conformal prediction, as well as a discussion on general implications for drug discovery.

Place, publisher, year, edition, pages
2021. Vol. 110, no 1, p. 42-49
Keywords [en]
QSAR, Conformal prediction, Predictive modeling, Confidence, Applicability domain
National Category
Computer and Information Sciences
Identifiers
URN: urn:nbn:se:su:diva-190083DOI: 10.1016/j.xphs.2020.09.055ISI: 000600571800007PubMedID: 33075380OAI: oai:DiVA.org:su-190083DiVA, id: diva2:1528775
Available from: 2021-02-16 Created: 2021-02-16 Last updated: 2022-02-25Bibliographically approved

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Norinder, Ulf

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