Efficient Online Transcription Factor Binding Site Adjustment by Integrating Transitive Graph Projection with MoRAine 2.0

UNLABELLED We investigated the problem of imprecisely determined prokaryotic transcription factor (TF) binding sites (TFBSs). We found that the identification and reinvestigation of questionable binding motifs may result in improved models of these motifs. Subsequent modelbased predictions of gene regulatory interactions may be performed with increased accuracy when the TFBSs annotation underlying these models has been re-adjusted. We present MoRAine 2.0, a significantly improved version of MoRAine. It can automatically identify cases of unfavorable TFBS strand annotations and imprecisely determined TFBS positions. With release 2.0, we close the gap between reasonable running time and high accuracy. Furthermore, it requires only minimal input from the user: (1) the input TFBS sequences and (2) the length of the flanking sequences. CONCLUSIONS MoRAine 2.0 is an easy-to-use, integrated, and publicly available web tool for the re-annotation of questionable TFBSs. It can be used online or downloaded as a stand-alone version from http://moraine.cebitec.uni-bielefeld.de.

[1]  J. Collado-Vides,et al.  Modular analysis of the transcriptional regulatory network of E. coli. , 2005, Trends in genetics : TIG.

[2]  Sebastian Böcker,et al.  Going weighted: Parameterized algorithms for cluster editing , 2009, Theor. Comput. Sci..

[3]  Dieter Jahn,et al.  Virtual Footprint and PRODORIC: an integrative framework for regulon prediction in prokaryotes , 2005, Bioinform..

[4]  E. Wingender,et al.  MATCH: A tool for searching transcription factor binding sites in DNA sequences. , 2003, Nucleic acids research.

[5]  Andreas Tauch,et al.  Towards the integrated analysis, visualization and reconstruction of microbial gene regulatory networks , 2008, Briefings Bioinform..

[6]  Christiane K. Kleindt,et al.  Integrated analysis and reconstruction of microbial transcriptional gene regulatory networks using CoryneRegNet , 2009, Nature Protocols.

[7]  M. Gerstein,et al.  Structure and evolution of transcriptional regulatory networks. , 2004, Current opinion in structural biology.

[8]  J. Baumbach,et al.  CoryneRegNet: An ontology-based data warehouse of corynebacterial transcription factors and regulatory networks , 2006, BMC Genomics.

[9]  L. Hellman,et al.  Electrophoretic mobility shift assay (EMSA) for detecting protein–nucleic acid interactions , 2007, Nature Protocols.

[10]  D. Galas,et al.  DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. , 1978, Nucleic acids research.

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

[12]  Martin Vingron,et al.  On the Power of Profiles for Transcription Factor Binding Site Detection , 2003, Statistical applications in genetics and molecular biology.

[13]  Zohar Yakhini,et al.  Clustering gene expression patterns , 1999, J. Comput. Biol..

[14]  R. Sauer,et al.  Transcription factors: structural families and principles of DNA recognition. , 1992, Annual review of biochemistry.

[15]  T. Wittkop,et al.  CoryneRegNet 2: An Integrative Bioinformatics Approach for Reconstruction and Comparison of Transcriptional Regulatory Networks in Prokaryotes , 2006 .

[16]  D. S. Chekmenev,et al.  P-Match: transcription factor binding site search by combining patterns and weight matrices , 2005, Nucleic Acids Res..

[17]  Sven Rahmann,et al.  MoRAine - A web server for fast computational transcription factor binding motif re-annotation , 2008, J. Integr. Bioinform..

[18]  Sven Rahmann,et al.  Large scale clustering of protein sequences with FORCE -A layout based heuristic for weighted cluster editing , 2007, BMC Bioinformatics.

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

[20]  S. Teichmann,et al.  Evolutionary dynamics of prokaryotic transcriptional regulatory networks. , 2006, Journal of molecular biology.

[21]  Michael Beckstette,et al.  Fast index based algorithms and software for matching position specific scoring matrices , 2006, BMC Bioinformatics.

[22]  Raja Jothi,et al.  Genome-wide identification of in vivo protein–DNA binding sites from ChIP-Seq data , 2008, Nucleic acids research.

[23]  Andreas Tauch,et al.  Reliable transfer of transcriptional gene regulatory networks between taxonomically related organisms , 2009, BMC Systems Biology.

[24]  Andreas Tauch,et al.  CoryneRegNet 3.0--an interactive systems biology platform for the analysis of gene regulatory networks in corynebacteria and Escherichia coli. , 2007, Journal of biotechnology.

[25]  J. Keilwagen,et al.  MotifAdjuster: a tool for computational reassessment of transcription factor binding site annotations , 2009, Genome Biology.

[26]  Jan Baumbach,et al.  CoryneRegNet 4.0 – A reference database for corynebacterial gene regulatory networks , 2007, BMC Bioinformatics.

[27]  Hongyu Zhao,et al.  Protein–DNA interaction mapping using genomic tiling path microarrays in Drosophila , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Alexander E. Kel,et al.  MATCHTM: a tool for searching transcription factor binding sites in DNA sequences , 2003, Nucleic Acids Res..