Using varying negative examples to improve computational predictions of transcription factor binding sites

The identification of transcription factor binding sites (TFBSs) is a non-trivial problem as the existing computational predictors produce a lot of false predictions. Though it is proven that combining these predictions with a meta-classifier, like Support Vector Machines (SVMs), can improve the overall results, this improvement is not as significant as expected. The reason for this is that the predictors are not reliable for the negative examples from non-binding sites in the promoter region. Therefore, using negative examples from different sources during training an SVM can be one of the solutions to this problem. In this study, we used different types of negative examples during training the classifier. These negative examples can be far away from the promoter regions or produced by randomisation or from the intronic region of genes. By using these negative examples during training, we observed their effect in improving predictions of TFBSs in the yeast. We also used a modified cross-validation method for this type of problem. Thus we observed substantial improvement in the classifier performance that could constitute a model for predicting TFBSs. Therefore, the major contribution of the analysis is that for the yeast genome, the position of binding sites could be predicted with high confidence using our technique and the predictions are of much higher quality than the predictions of the original prediction algorithms.