The effect of orthology and coregulation on detecting regulatory motifs.
BACKGROUND
Computational de novo discovery of transcription factor binding sites is still a challenging problem. The growing number of sequenced genomes allows integrating orthology evidence with coregulation information when searching for motifs. Moreover, the more advanced motif detection algorithms explicitly model the phylogenetic relatedness between the orthologous input sequences and thus should be well adapted towards using orthologous information. In this study, we evaluated the conditions under which complementing coregulation with orthologous information improves motif detection for the class of probabilistic motif detection algorithms with an explicit evolutionary model.


METHODS
We designed datasets (real and synthetic) covering different degrees of coregulation and orthologous information to test how well Phylogibbs and Phylogenetic sampler, as representatives of the motif detection algorithms with evolutionary model performed as compared to MEME, a more classical motif detection algorithm that treats orthologs independently.


CONCLUSIONS
Under certain conditions detecting motifs in the combined coregulation-orthology space is indeed more efficient than using each space separately, but this is not always the case. Moreover, the difference in success rate between the advanced algorithms and MEME is still marginal. The success rate of motif detection depends on the complex interplay between the added information and the specificities of the applied algorithms. Insights in this relation provide information useful to both developers and users. All benchmark datasets are available at http://homes.esat.kuleuven.be/~kmarchal/Supplementary_Storms_Valerie_PlosONE.
CMPG, Department of Microbial and Molecular Systems, Katholieke Universiteit Leuven, Leuven, Belgium.
Valerie
V
Storms
Marleen
M
Claeys
Aminael
A
Sanchez
Bart
B
De Moor
Annemieke
A
Verstuyf
Kathleen
K
Marchal
D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D020563:Gammaproteobacteria / Q000145:classification / Q000235:genetics; D008957:Models, Genetic; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012440:Saccharomyces / Q000145:classification / Q000235:genetics; D012984:Software; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors