When either of the two types of method is used to scan an entire genome, or the promoter regions of a genome, there is a difficult trade-off between sensitivity and specificity. If the threshold for a prediction (sites above a chosen information measure cutoff, or below a chosen p-value level) is chosen so as to reflect a reasonably low false positive rate (i.e., high specificity), it is frequently difficult to recover many of the known transcription factor binding sites that were used in the construction of the motif. Conversely, the choice of a threshold for prediction that finds many of the known transcription factor binding sites (i.e., high sensitivity) invariably leads to an overwhelming number of additional predicted sites, most of which are likely false positives. (Generally, we do not know where a transcription factor might bind in a way that does not affect transcription and thus, in this latter case, the functional interpretation of these "false positives" is somewhat subtle.)