CircularLogo: A lightweight web application to visualize intra-motif dependencies

BackgroundThe sequence logo has been widely used to represent DNA or RNA motifs for more than three decades. Despite its intelligibility and intuitiveness, the traditional sequence logo is unable to display the intra-motif dependencies and therefore is insufficient to fully characterize nucleotide motifs. Many methods have been developed to quantify the intra-motif dependencies, but fewer tools are available for visualization.ResultWe developed CircularLogo, a web-based interactive application, which is able to not only visualize the position-specific nucleotide consensus and diversity but also display the intra-motif dependencies. Applying CircularLogo to HNF6 binding sites and tRNA sequences demonstrated its ability to show intra-motif dependencies and intuitively reveal biomolecular structure. CircularLogo is implemented in JavaScript and Python based on the Django web framework. The program’s source code and user’s manual are freely available at http://circularlogo.sourceforge.net. CircularLogo web server can be accessed from http://bioinformaticstools.mayo.edu/circularlogo/index.html.ConclusionCircularLogo is an innovative web application that is specifically designed to visualize and interactively explore intra-motif dependencies.

[1]  V A Erdmann,et al.  Role of the D arm and the anticodon arm in tRNA recognition by eubacterial and eukaryotic RNase P enzymes. , 1993, Biochemistry.

[2]  Morten Nielsen,et al.  Seq2Logo: a method for construction and visualization of amino acid binding motifs and sequence profiles including sequence weighting, pseudo counts and two-sided representation of amino acid enrichment and depletion , 2012, Nucleic Acids Res..

[3]  Wyeth W. Wasserman,et al.  The Next Generation of Transcription Factor Binding Site Prediction , 2013, PLoS Comput. Biol..

[4]  M Yarus,et al.  Transfer RNA structure and coding specificity. I. Evidence that a D-arm mutation reduces tRNA dissociation from the ribosome. , 1989, Journal of molecular biology.

[5]  Sean R. Eddy,et al.  Rfam: an RNA family database , 2003, Nucleic Acids Res..

[6]  Michael T. Zimmermann,et al.  MACE: model based analysis of ChIP-exo , 2014, Nucleic acids research.

[7]  Jens Keilwagen,et al.  A general approach for discriminative de novo motif discovery from high-throughput data , 2013, GCB.

[8]  Wilfried Haerty,et al.  Genome-wide discovery of human splicing branchpoints , 2015, Genome research.

[9]  Gary D. Stormo,et al.  DNA binding sites: representation and discovery , 2000, Bioinform..

[10]  G. Stormo,et al.  Improved Models for Transcription Factor Binding Site Identification Using Nonindependent Interactions , 2012, Genetics.

[11]  Ivo Grosse,et al.  Inferring intra-motif dependencies of DNA binding sites from ChIP-seq data , 2015, BMC Bioinformatics.

[12]  G. Stormo,et al.  Non-independence of Mnt repressor-operator interaction determined by a new quantitative multiple fluorescence relative affinity (QuMFRA) assay. , 2001, Nucleic acids research.

[13]  G. Crooks,et al.  WebLogo: a sequence logo generator. , 2004, Genome research.

[14]  Qing Zhou,et al.  Modeling within-motif dependence for transcription factor binding site predictions , 2004, Bioinform..

[15]  George M Church,et al.  pLogo: a probabilistic approach to visualizing sequence motifs , 2013, Nature Methods.

[16]  Valentina Boeva,et al.  Analysis of Genomic Sequence Motifs for Deciphering Transcription Factor Binding and Transcriptional Regulation in Eukaryotic Cells , 2016, Front. Genet..

[17]  D. Rio,et al.  Mechanisms and Regulation of Alternative Pre-mRNA Splicing. , 2015, Annual review of biochemistry.

[18]  J. Keilwagen,et al.  On the Value of Intra-Motif Dependencies of Human Insulator Protein CTCF , 2014, PloS one.

[19]  G. Church,et al.  Nucleotides of transcription factor binding sites exert interdependent effects on the binding affinities of transcription factors. , 2002, Nucleic acids research.

[20]  Daniel E. Newburger,et al.  Diversity and Complexity in DNA Recognition by Transcription Factors , 2009, Science.

[21]  Gary D. Stormo,et al.  enoLOGOS: a versatile web tool for energy normalized sequence logos , 2005, Nucleic Acids Res..

[22]  Liam Paninski,et al.  Estimation of Entropy and Mutual Information , 2003, Neural Computation.

[23]  Chuan-Hsiung Chang,et al.  Exploring comprehensive within-motif dependence of transcription factor binding in Escherichia coli , 2015, Scientific reports.

[24]  Jens Keilwagen,et al.  Varying levels of complexity in transcription factor binding motifs , 2015, Nucleic acids research.

[25]  Eckart Bindewald,et al.  CorreLogo: an online server for 3D sequence logos of RNA and DNA alignments , 2006, Nucleic Acids Res..