On the other hand, the window size must be large enough to provide significant word counts, a requirement that strengthens with the size of the words under consideration and the intrinsic variability of the genomic signature along the genome. All together, the trade-off that has been implemented in this paper allows detecting atypical regions as small as 1 kb. In fact, rRNA regions sharing this characteristic were consistently detected. It must be pointed out that smaller fragments can be eventually detected if their signatures are radically atypical. G+C% atypicality has often been considered as criterion for detecting HTs (8, 24) , but this approach suffered several drawbacks (28) (29) (30) . It is to be noted that our signature-based method detects regions for which the G+C% lies within one standard deviation from the mean G+C% of the species (for instance, regions 2675251-2676250 in B.subtilis or 534751-535250 in H.Influenzae, see also Supplementary Materials 2 and 4).