TRStalker: an efficient heuristic for finding fuzzy tandem repeats

Motivation: Genomes in higher eukaryotic organisms contain a substantial amount of repeated sequences. Tandem Repeats (TRs) constitute a large class of repetitive sequences that are originated via phenomena such as replication slippage and are characterized by close spatial contiguity. They play an important role in several molecular regulatory mechanisms, and also in several diseases (e.g. in the group of trinucleotide repeat disorders). While for TRs with a low or medium level of divergence the current methods are rather effective, the problem of detecting TRs with higher divergence (fuzzy TRs) is still open. The detection of fuzzy TRs is propaedeutic to enriching our view of their role in regulatory mechanisms and diseases. Fuzzy TRs are also important as tools to shed light on the evolutionary history of the genome, where higher divergence correlates with more remote duplication events. Results: We have developed an algorithm (christened TRStalker) with the aim of detecting efficiently TRs that are hard to detect because of their inherent fuzziness, due to high levels of base substitutions, insertions and deletions. To attain this goal, we developed heuristics to solve a Steiner version of the problem for which the fuzziness is measured with respect to a motif string not necessarily present in the input string. This problem is akin to the 'generalized median string' that is known to be an NP-hard problem. Experiments with both synthetic and biological sequences demonstrate that our method performs better than current state of the art for fuzzy TRs and that the fuzzy TRs of the type we detect are indeed present in important biological sequences. Availability: TRStalker will be integrated in the web-based TRs Discovery Service (TReaDS) at bioalgo.iit.cnr.it. Contact: marco.pellegrini@iit.cnr.it Supplementary information: Supplementary data are available at Bioinformatics online.