Discovery and annotation of cis regulatory elements has always been a daunting task. Completion of many genome projects have opened new opportunities for discovering cis regulatory elements by comparitive genomics. If orthologus promoter sequences show same putative binding sites, then they are considered to be functional.The major drawback of present motif discovery methods is that they are based of pregenerated multiple alignments and they do not work for diverged species like plants. As a result motifs present in misalignments go undetected.
Witte et. al.(2015) have proposed an algorithm which is based on alignment based as well as alignment free motif discovery. Confidence score is calculated for putative motifs. They have applied the new method for four monocot species.The software has been written in Java.Source code. For instruction manual you can visit the following site http://bioinformatics.intec.ugent.be/blsspeller
Reference
Witte D.D.et al. (2015) BLSSpellar:exhaustive Comparitive Discovery of conserved cis regulatory elements.Bioinformatics 31(23)3758-3766