The prediction of bacterial transcription start sites using SVMs

Identifying promoters is the key to understanding gene expression in bacteria. Promoters lie in tightly constrained positions relative to the transcription start site (TSS). In this paper, we address the problem of predicting transcription start sites in Escherichia coli. Knowing the TSS position, one can then predict the promoter position to within a few base pairs, and vice versa. The accepted method for promoter prediction is to use a pair of position weight matrices (PWMs), which define conserved motifs at the sigma-factor binding site. However this method is known to result in a large number of false positive predictions, thereby limiting its usefulness to the experimental biologist. We adopt an alternative approach based on the Support Vector Machine (SVM) using a modified mismatch spectrum kernel. Our modifications involve tagging the motifs with their location, and selectively pruning the feature set. We quantify the performance of several SVM models and a PWM model using a performance metric of area under the detection-error tradeoff (DET) curve. SVM models are shown to outperform the PWM on a biologically realistic TSS prediction task. We also describe a more broadly applicable peak scoring technique which reduces the number of false positive predictions, greatly enhancing the utility of our results.