Genetic algorithm for dimer-led and error-restricted spaced motif discovery

Abstract

DNA motif discovery is an important problem for deciphering protein-DNA bindings in gene regulation. To discover generic spaced motifs which have multiple conserved patterns separated by wild-cards called spacers, the genetic algorithm (GA) based GASMEN has been proposed and shown to outperform related methods. However, the over-generic modeling of any number of spacers increases the optimization difficulty in practice. In protein-DNA binding case studies, complicated spaced motifs are rare while dimers with single spacers are more common spaced motifs. Moreover, errors (mismatches) in a conserved pattern are not arbitrarily distributed as certain highly conserved nucleotides are essential to maintain bindings. Motivated by better optimization in real applications, we have developed a new method, which is GA for Dimer-led and Error-restricted Spaced Motifs (GADESM). Common spaced motifs are paid special attention to using dimer-led initialization in the population initialization. The results on real datasets show that the dimer-led initialization in GADESM achieves better fitness than GASMEN with statistical significance. With additional error-restricted motif occurrence retrieval, GADESM has shown better performance than GASMEN on both comprehensive simulation data and a real ChIP-seq case study.