PMC:1570465 / 4525-5867 JSONTXT

{"project":"2_test","denotations":[{"id":"16916460-2006136-1687066","span":{"begin":439,"end":441},"obj":"2006136"},{"id":"16916460-15297295-1687067","span":{"begin":643,"end":645},"obj":"15297295"},{"id":"16916460-11410653-1687068","span":{"begin":985,"end":987},"obj":"11410653"},{"id":"16916460-11861919-1687069","span":{"begin":988,"end":990},"obj":"11861919"},{"id":"16916460-15297295-1687070","span":{"begin":1252,"end":1254},"obj":"15297295"},{"id":"16916460-16455748-1687071","span":{"begin":1338,"end":1340},"obj":"16455748"}],"text":"Here, we introduce a combinatorial optimization framework for motif finding that is flexible enough to model several variants of the problem and is not limited by the motif length. Underlying our approach, we consider motif discovery as the problem of finding the best gapless local multiple sequence alignment using the sum-of-pairs (SP) scoring scheme. The SP-score is one of many reasonable schemes for assessing motif conservation [30,31]. In the case of motif search, where the goal is to use a set of known motif instances and uncover additional instances, the SP-score has been shown empirically to be comparable to PSSM-based methods [32]. Additionally, unlike the PSSM models, which typically assume independence of motif positions, the SP-score can address the problem of nucleotide or amino acid dependencies in a natural way. This is an important consideration; for example in the case of nucleotides, it has been shown that there are interdependent effects between bases [33,34]. Moreover, modeling these dependencies using the SP-score leads to improved performance in representing and searching for binding sites; a similar statistically significant improvement is not observed when extending PSSMs to incorporate pairwise dependencies [32]. The SP-score was most recently utilized in the context of motif finding in MaMF [13]."}