Machine learning-based prediction of drug-drug interactions by integrating drug phenotypic, therapeutic, chemical, and genomic properties.

Cheng F, Zhao Z
J Am Med Inform Assoc. 2014 21 (e2): e278-86

PMID: 24644270 · PMCID: PMC4173180 · DOI:10.1136/amiajnl-2013-002512

OBJECTIVE - Drug-drug interactions (DDIs) are an important consideration in both drug development and clinical application, especially for co-administered medications. While it is necessary to identify all possible DDIs during clinical trials, DDIs are frequently reported after the drugs are approved for clinical use, and they are a common cause of adverse drug reactions (ADR) and increasing healthcare costs. Computational prediction may assist in identifying potential DDIs during clinical trials.

METHODS - Here we propose a heterogeneous network-assisted inference (HNAI) framework to assist with the prediction of DDIs. First, we constructed a comprehensive DDI network that contained 6946 unique DDI pairs connecting 721 approved drugs based on DrugBank data. Next, we calculated drug-drug pair similarities using four features: phenotypic similarity based on a comprehensive drug-ADR network, therapeutic similarity based on the drug Anatomical Therapeutic Chemical classification system, chemical structural similarity from SMILES data, and genomic similarity based on a large drug-target interaction network built using the DrugBank and Therapeutic Target Database. Finally, we applied five predictive models in the HNAI framework: naive Bayes, decision tree, k-nearest neighbor, logistic regression, and support vector machine, respectively.

RESULTS - The area under the receiver operating characteristic curve of the HNAI models is 0.67 as evaluated using fivefold cross-validation. Using antipsychotic drugs as an example, several HNAI-predicted DDIs that involve weight gain and cytochrome P450 inhibition were supported by literature resources.

CONCLUSIONS - Through machine learning-based integration of drug phenotypic, therapeutic, structural, and genomic similarities, we demonstrated that HNAI is promising for uncovering DDIs in drug development and postmarketing surveillance.

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MeSH Terms (12)

Artificial Intelligence Bayes Theorem Decision Trees Drug Interactions Humans Logistic Models Models, Theoretical Molecular Structure Pharmaceutical Preparations Pharmacokinetics ROC Curve Support Vector Machine

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