title: A discriminative approach for unsupervised clustering of DNA sequence motifs.
abstract: Algorithmic comparison of DNA sequence motifs is a problem in bioinformatics that has received increased attention during the last years. Its main applications concern characterization of potentially novel motifs and clustering of a motif collection in order to remove redundancy. Despite growing interest in motif clustering, the question which motif clusters to aim at has so far not been systematically addressed. Here we analyzed motif similarities in a comprehensive set of vertebrate transcription factor classes. For this we developed enhanced similarity scores by inclusion of the information coverage (IC) criterion, which evaluates the fraction of information an alignment covers in aligned motifs. A network-based method enabled us to identify motif clusters with high correspondence to DNA-binding domain phylogenies and prior experimental findings. Based on this analysis we derived a set of motif families representing distinct binding specificities. These motif families were used to train a classifier which was further integrated into a novel algorithm for unsupervised motif clustering. Application of the new algorithm demonstrated its superiority to previously published methods and its ability to reproduce entrained motif families. As a result, our work proposes a probabilistic approach to decide whether two motifs represent common or distinct binding specificities.
authors.affiliation: Biobase GmbH, Wolfenbüttel, Germany. philip.stegmaier@genexplain.com
authors.forename: Philip
authors.initials: P
authors.lastname: Stegmaier
authors.forename: Alexander
authors.initials: A
authors.lastname: Kel
authors.forename: Edgar
authors.initials: E
authors.lastname: Wingender
authors.forename: Jürgen
authors.initials: J
authors.lastname: Borlak
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D030541:Databases, Genetic; D053263:Gene Regulatory Networks; D016015:Logistic Models; D059372:Nucleotide Motifs; D010802:Phylogeny; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D004247:DNA
references.citation: Mol Cell Biol. 1995 May;15(5):2582-8
references.pmid: 7739539
references.citation: Proc Natl Acad Sci U S A. 1994 May 10;91(10):4175-9
references.pmid: 8183888
references.citation: Science. 2000 Dec 22;290(5500):2306-9
references.pmid: 11125145
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D102-6
references.pmid: 18006571
references.citation: BMC Genomics. 2007 Oct 18;8:378
references.pmid: 17945028
references.citation: Science. 2007 Jun 8;316(5830):1497-502
references.pmid: 17540862
references.citation: Eur J Biochem. 1995 Oct 1;233(1):73-82
references.pmid: 7588776
references.citation: Bioinformatics. 2005 Apr 1;21(7):951-60
references.pmid: 15531603
references.citation: Mol Biol (Mosk). 1997 Jul-Aug;31(4):584-600
references.pmid: 9340487
references.citation: PLoS One. 2010 Jan 20;5(1):e8797
references.pmid: 20098703
references.citation: Cell. 1999 Apr 16;97(2):161-3
references.pmid: 10219237
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D108-10
references.pmid: 16381825
references.citation: Bioinformatics. 1998;14(3):244-51
references.pmid: 9614267
references.citation: BMC Bioinformatics. 2009 Jul 20;10:224
references.pmid: 19615102
references.citation: Nucleic Acids Res. 1999 Jan 1;27(1):318-22
references.pmid: 9847216
references.citation: Bioinformatics. 2002 Mar;18(3):502-4
references.pmid: 11934758
references.citation: J Mol Biol. 2004 Apr 23;338(2):207-15
references.pmid: 15066426
references.citation: BMC Bioinformatics. 2007 Jun 08;8:189
references.pmid: 17559640
references.citation: Bioinformatics. 2005 Feb 1;21(3):307-13
references.pmid: 15319260
references.citation: Genome Res. 2004 Jun;14(6):1188-90
references.pmid: 15173120
references.citation: PLoS Comput Biol. 2008 Feb 29;4(2):e1000010
references.pmid: 18463706
references.citation: PLoS Comput Biol. 2007 Mar 30;3(3):e61
references.pmid: 17397256
references.citation: Genome Inform. 2004;15(2):276-86
references.pmid: 15706513
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W253-8
references.pmid: 17478497
references.citation: Plant J. 1997 Apr;11(4):703-15
references.pmid: 9161031
references.citation: Bioinformatics. 2008 Feb 1;24(3):350-7
references.pmid: 18174183
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W438-41
references.pmid: 15980506
references.citation: Genome Biol. 2007;8(2):R24
references.pmid: 17324271
references.citation: BMC Bioinformatics. 2005 Sep 28;6:237
references.pmid: 16191190