Here R 1 (w k ) and R 2 (w k ) represent the rank of a specific n-tuple, w k , in sequences S 1 and S 2 , respectively. N = 2 n is the number of different n-tuple sequences (or patterns). The absolute difference of The mapping procedure for a n-tuple binary symbolic sequence (here n = 6 for illustrative purposes) from part of an interbeat interval time series. (B) Rank-order comparison of two interbeat interval time series from the two healthy subjects, using 6tuple binary symbolic mapping. In this case, frequencies of 2 6 = 64 6tuple symbolic patterns were determined and ranked accordingly. For each 6-tuple symbolic sequence (black dot), its rank in subject A is plotted against its rank in subject B. The dashed diagonal line indicates the case where the rank order of 6-tuple symbolic sequence for both subjects is identical. doi:10.1371/journal.pone.0019232.g001 ranks, R 1 (w k ){R 2 (w k ) j j , is weighted by summing Shannon's entropy H for w k in sequences S 1 and S 2 [44] . Shannon's entropy measures the information richness of each n-tuple in both sequences. Thus, the more frequently used n-tuples contribute more to measuring similarity among symbolic sequences. Of note, the IBS is an empirical index which does not necessarily obey the triangular inequality criterion of a distance measure. Therefore, the triangular inequality test is required before generating a cluster [16, 17] . The IBS algorithm was available at Physionet (http:// www.physionet.org/physiotools/ibs/).