Article

LASAGNA: A novel algorithm for transcription factor binding site alignment

BMC Bioinformatics (Impact Factor: 2.67). 03/2013; 14(1):108. DOI: 10.1186/1471-2105-14-108
Source: PubMed

ABSTRACT Background Scientists routinely scan DNA sequences for transcription factor (TF) binding sites (TFBSs). Most of the available tools rely on position-specific scoring matrices (PSSMs) constructed from aligned binding sites.Because of the resolutions of assays used to obtain TFBSs, databases such as TRANSFAC, ORegAnno and PAZARstore unaligned variable-length DNA segments containing binding sites of a TF. These DNA segments need to bealigned to build a PSSM. While the TRANSFAC database provides scoring matrices for TFs, nearly 78% of the TFsin the public release do not have matrices available. As work on TFBS alignment algorithms has been limited, itis highly desirable to have an alignment algorithm tailored to TFBSs.Results We designed a novel algorithm named LASAGNA, which is aware of the lengths of input TFBSs and utilizes position dependence.Results on 189 TFs of 5 species in the TRANSFAC database showed that our method significantly outperformed ClustalW2and MEME. We further compared a PSSM method dependent on LASAGNA to an alignment-free TFBS search method.Results on 89 TFs whose binding sites can be located in genomes showed that our method is significantly more preciseat fixed recall rates. Finally, we described LASAGNA-ChIP, a more sophisticated version for ChIP(Chromatin immunoprecipitation) experiments. Under the one-per-sequence model, it showed comparableperformance with MEME in discovering motifs in ChIP-seq peak sequences.Conclusions We conclude that the LASAGNA algorithm is simple and effective in aligning variable-length binding sites.It has been integrated into a user-friendly webtool for TFBS search and visualization calledLASAGNA-Search. The tool currently stores precomputed PSSM models for 189 TFs and 133 TFs built from TFBSs in theTRANSFAC Public database (release 7.0) and the ORegAnno database (08Nov10 dump), respectively.The webtool is available at: http://biogrid.engr.uconn.edu/lasagna_search/.

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Available from: Chun-Hsi Huang, May 16, 2015
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