Data mining PubChem using a support vector machine with the Signature molecular descriptor: classification of factor XIa inhibitors

J Mol Graph Model. 2008 Nov;27(4):466-75. doi: 10.1016/j.jmgm.2008.08.004. Epub 2008 Aug 27.


The amount of high-throughput screening (HTS) data readily available has significantly increased because of the PubChem project ( There is considerable opportunity for data mining of small molecules for a variety of biological systems using cheminformatic tools and the resources available through PubChem. In this work, we trained a support vector machine (SVM) classifier using the Signature molecular descriptor on factor XIa inhibitor HTS data. The optimal number of Signatures was selected by implementing a feature selection algorithm of highly correlated clusters. Our method included an improvement that allowed clusters to work together for accuracy improvement, where previous methods have scored clusters on an individual basis. The resulting model had a 10-fold cross-validation accuracy of 89%, and additional validation was provided by two independent test sets. We applied the SVM to rapidly predict activity for approximately 12 million compounds also deposited in PubChem. Confidence in these predictions was assessed by considering the number of Signatures within the training set range for a given compound, defined as the overlap metric. To further evaluate compounds identified as active by the SVM, docking studies were performed using AutoDock. A focused database of compounds predicted to be active was obtained with several of the compounds appreciably dissimilar to those used in training the SVM. This focused database is suitable for further study. The data mining technique presented here is not specific to factor XIa inhibitors, and could be applied to other bioassays in PubChem where one is looking to expand the search for small molecules as chemical probes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / classification*
  • Factor XIa / antagonists & inhibitors*
  • Factor XIa / metabolism
  • Models, Molecular
  • Molecular Structure
  • Software


  • Enzyme Inhibitors
  • Factor XIa