W438–W441 Nucleic Acids Research, 2005, Vol. 33, Web Server issue doi:10.1093/nar/gki590 T-Reg Comparator: an analysis tool for the comparison of position weight matrices Stefan Roepcke*, Steffen Grossmann, Sven Rahmann1 and Martin Vingron Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany and 1Department of Genome Informatics, University of Bielefeld, 33594 Bielefeld, Germany Received February 14, 2005; Revised April 19, 2005; Accepted May 3, 2005 ABSTRACT T-Reg Comparator is a novel software tool designed to support research into transcriptional regulation. Sequence motifs representing transcription factor binding sites are usually encoded as position weight matrices. The user inputs a set of such weight matrices or binding site sequences and our program matches them against the T-Reg database, which is presently built on data from the Transfac [E. Wingender (2004) In Silico Biol., 4, 55–61] and Jaspar [A. Sandelin, W. Alkema, P. Engstrom, W. W. Wasserman and B. Lenhard (2004) Nucleic Acids Res., 32, D91–D94]. Our tool delivers a detailed report on similarities between user-supplied motifs and motifs in the database. Apart from simple one-to-one relationships, T-Reg Comparator is also able to detect similarities between submatrices. In addition, we provide a user interface to a program for sequence scanning with weight matrices. Typical areas of application for T-Reg Comparator are motif and regulatory module finding and annota- tion of regulatory genomic regions. T-Reg Com- parator is available at http://treg.molgen.mpg.de. INTRODUCTION The binding of transcription factors to target DNA in a sequence-speciﬁc manner is a key step in transcriptional regulation. Binding afﬁnities of transcription factors are often described by position weight matrices (PWMs). These matrices specify the sequence motif by giving a base distri- bution for each of its positions. Transfac and Jaspar (1,2) are two well-recognized projects that aim at giving comprehens- ive collections of eukaryotic transcription factors and descrip- tions of their respective binding afﬁnities in terms of PWMs. In order to understand the binding speciﬁcity of transcription factors, it is essential to be able to relate newly derived motifs to the existing collections. Our work supports the comparison of weight matrices. Various large-scale approaches are nowadays available for identifying novel binding sites. A typical bioinformatics ana- lysis might encompass a search for over-represented sequence motifs in the promoters of co-regulated genes, e.g. based on a software package such as MEME (3). Likewise, wet-lab tech- niques including SELEX (4) and chromatin immunoprecipita- tion (5,6) may provide data from which PWMs are derived. The growing number of PWMs leads to the problem of dis- tinguishing new from old: for a newly derived PWM it is not immediately clear whether it describes an already known bind- ing site or whether it is actually new information. This problem is further aggravated by the fact that the binding speciﬁcity of many transcription factors is not very pronounced. In practice, available PWMs can be very short (4–6 positions) or can contain a substantial number of uninformative positions. For some well-studied transcription factors several highly similar PWMs are reported in Transfac. Recent papers describe a number of comparison methods for weight matrices (7–10). Schones and co-authors focus on the question of determining the most adequate measure of simil- arity (7). They restrict each matrix to a core part and base their method on the product-multinomial distribution. Sandelin and Wasserman cluster the weight matrices of Jaspar and propose a grouping into familial binding proﬁles (8). In two papers by the group of De Moor a similarity measure based on the Kullback–Leiber distance has been used to compare weight matrices (9,10). Our web application T-Reg Comparator is dedicated to supporting studies into transcriptional regulation. Lists of motifs can be compared against weight matrices in the T-Reg database, which currently contains all PWMs from Transfac and Jaspar (1,2). For convenience we facilitate the input of sets of binding sites or alignments as well. An import- ant feature of our tool is that partially overlapping but high- scoring matches are recognized as well. A detailed report tells the user whether the identiﬁed motif is novel or resembles the binding site of some known transcription factor. In addition, *To whom correspondence should be addressed. Tel: +49 30 84131159; Fax: +49 30 84131152; Email: roepcke@molgen.mpg.de The Author 2005. Published by Oxford University Press. All rights reserved. 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