Position-specific substitutions Here we allow a position (a DNA symbol) in the instance motif ℳ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2yHvtyaeHbnfgDOvwBHrxAJfwnaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaWaaeGaeaaakeaaimaacqWFZestaaa@3790@ to be substituted with 1 or 2 other DNA symbols. All such neighbors will contribute to the frequency of ℳ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2yHvtyaeHbnfgDOvwBHrxAJfwnaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaWaaeGaeaaakeaaimaacqWFZestaaa@3790@. For example, for ℳ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2yHvtyaeHbnfgDOvwBHrxAJfwnaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaWaaeGaeaaakeaaimaacqWFZestaaa@3790@ = ACG[4,6]TT, if we allow e1 = 1 substitutions in motif M1 = ACG, at position 2, then AAG[4,6]TT, ACG[4,6]TT or AGG[4,6]TT may contribute to the frequency of ℳ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2yHvtyaeHbnfgDOvwBHrxAJfwnaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaWaaeGaeaaakeaaimaacqWFZestaaa@3790@. Instead of enumerating all of these separately, EXMOTIF can directly mine relevant motifs using IUPAC symbols (see Table 3). EXMOTIF simply constructs the pos-lists for the relevant IUPAC symbols by scanning sequences in S MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2yHvtyaeHbnfgDOvwBHrxAJfwnaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaWaaeGaeaaakeaaimaacqWFse=uaaa@3845@ once. Then it mines the motif instances as in the basic approach, since all allowed substitutions have already been incorporated into the relevant IUPAC symbols. Let vi, 1 ≤ i ≤ k, to denote the set of IUPAC symbols that can appear in the motif. When vi = 1 (i.e., each position allows only 1 DNA symbol), the alphabet used is {A, C, G, T}; when vi = 2 (i.e., each position may allow up to 2 DNA symbols), the expanded alphabet is {A, C, G, T, R, Y, K, M, S, W}; and when vi = 3 (i.e., each position may allow up to 3 DNA symbols), the expanded alphabet is {A, C, G, T, R, Y, K, M, S, W, B, D, H, V}. For example, when v1 = 2, instead of reporting ℳ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBamrtHrhAL1wy0L2yHvtyaeHbnfgDOvwBHrxAJfwnaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaWaaeGaeaaakeaaimaacqWFZestaaa@3790@ = ACG[4,6]TT as the mined instance, EXMOTIF may report ASG[4,6]TT as an instance, where S stands for either C or G (see Table 3). EXMOTIF also allows the user to specify the maximum number of IUPAC symbols that can appear in each simple motif, ei, 1 ≤ i ≤ k. Table 3 IUPAC alphabet (ΣIUPAC). Symbol A C G T Bases A C G T Symbol U R Y K Bases U A,G C,T G,T Symbol M S W B Bases A,C G,C A,T C,G,T Symbol D H V N Bases A,G,T A,C,T A,C,G A,C,G,T