Drug-drug interaction through molecular structure similarity analysis.
BACKGROUND
Drug-drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very challenging. Currently, the US Food and Drug Administration and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs.


METHODS
We present a new methodology applicable on a large scale that identifies novel DDIs based on molecular structural similarity to drugs involved in established DDIs. The underlying assumption is that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. DrugBank was used as a resource for collecting 9454 established DDIs. The structural similarity of all pairs of drugs in DrugBank was computed to identify DDI candidates.


RESULTS
The methodology was evaluated using as a gold standard the interactions retrieved from the initial DrugBank database. Results demonstrated an overall sensitivity of 0.68, specificity of 0.96, and precision of 0.26. Additionally, the methodology was also evaluated in an independent test using the Micromedex/Drugdex database.


CONCLUSIONS
The proposed methodology is simple, efficient, allows the investigation of large numbers of drugs, and helps highlight the etiology of DDI. A database of 58 403 predicted DDIs with structural evidence is provided as an open resource for investigators seeking to analyze DDIs.
Department of Biomedical Informatics, Columbia University Medical Center, New York, NY, USA. qosanti@yahoo.es
Santiago
S
Vilar
Rave
R
Harpaz
Eugenio
E
Uriarte
Lourdes
L
Santana
Raul
R
Rabadan
Carol
C
Friedman
D062313:Databases, Pharmaceutical; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D005544:Forecasting; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000145:classification; D060735:Pharmacovigilance; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014481:United States
D004364:Pharmaceutical Preparations