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HeliCis: a DNA motif discovery tool for colocalized motif pairs with periodic spacing.

Larsson E, Lindahl P, Mostad P - BMC Bioinformatics (2007)

Bottom Line: We show on simulated data that it can efficiently capture the synergistic effects of colocalization and periodic spacing to improve detection of weak DNA motifs.It provides a simple to use web interface which interactively visualizes the current settings and thereby makes it easy to understand the parameters and the model structure.HeliCis provides simple and efficient de novo discovery of colocalized DNA motif pairs, with or without periodic spacing.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wallenberg Laboratory for Cardiovascular Research, Bruna Stråket 16, Sahlgrenska University Hospital, SE-413 45 Göteborg, SWEDEN. erik.larsson@wlab.gu.se

ABSTRACT

Background: Correct temporal and spatial gene expression during metazoan development relies on combinatorial interactions between different transcription factors. As a consequence, cis-regulatory elements often colocalize in clusters termed cis-regulatory modules. These may have requirements on organizational features such as spacing, order and helical phasing (periodic spacing) between binding sites. Due to the turning of the DNA helix, a small modification of the distance between a pair of sites may sometimes drastically disrupt function, while insertion of a full helical turn of DNA (10-11 bp) between cis elements may cause functionality to be restored. Recently, de novo motif discovery methods which incorporate organizational properties such as colocalization and order preferences have been developed, but there are no tools which incorporate periodic spacing into the model.

Results: We have developed a web based motif discovery tool, HeliCis, which features a flexible model which allows de novo detection of motifs with periodic spacing. Depending on the parameter settings it may also be used for discovering colocalized motifs without periodicity or motifs separated by a fixed gap of known or unknown length. We show on simulated data that it can efficiently capture the synergistic effects of colocalization and periodic spacing to improve detection of weak DNA motifs. It provides a simple to use web interface which interactively visualizes the current settings and thereby makes it easy to understand the parameters and the model structure.

Conclusion: HeliCis provides simple and efficient de novo discovery of colocalized DNA motif pairs, with or without periodic spacing. Our evaluations show that it can detect weak periodic patterns which are not easily discovered using a sequential approach, i.e. first finding the binding sites and second analyzing the properties of their pairwise distances.

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Schematic drawing of the model structure. The triangle and rectangle represent the first and second motif respectively. Gray boxes indicate valid locations for the second motif given the position of the first. The "phase" (distance offset) is assumed to be constant over all sequences and is determined by the algorithm.
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Figure 1: Schematic drawing of the model structure. The triangle and rectangle represent the first and second motif respectively. Gray boxes indicate valid locations for the second motif given the position of the first. The "phase" (distance offset) is assumed to be constant over all sequences and is determined by the algorithm.

Mentions: We propose a de novo method for motif discovery, HeliCis, which can find motif pairs separated by a distance (gap) that varies in a periodical manner. More specifically, the distance is modeled as some fixed offset φ (the phase) plus a variable integer multiple of the period T (Figure 1). Small deviations from exact periodic spacing may optionally be allowed. HeliCis detects patterns which are common to a group of sequences. A typical input would be regulatory DNA from a set of assumedly coregulated genes. The motif pair is assumed to be either present or absent in each sequence and may optionally be allowed to occur on either strand. The period T is specified by the user, but the program can be provided with a range of periods to evaluate. Upper and lower boundaries for the distance can be specified. The distance can be allowed to be negative, making it possible to find unordered motif pairs. Our method is not limited to finding periodically distributed binding sites. The flexibility of the algorithm makes the task of finding colocalized motifs (e.g. positioned within 100 bp of one another without periodicity) or motifs with fixed spacing (e.g. always exactly 25 bp from each other) into special cases simply achieved by choosing appropriate parameters. E.g. by setting the period to one, the model will find colocalized motifs without periodicity. Examples of parameter settings for different scenarios are available on the HeliCis home page[20]. The software also incorporates the possibility to take advantage of interspecies conservation by favoring motif placement in highly conserved regions.


HeliCis: a DNA motif discovery tool for colocalized motif pairs with periodic spacing.

Larsson E, Lindahl P, Mostad P - BMC Bioinformatics (2007)

Schematic drawing of the model structure. The triangle and rectangle represent the first and second motif respectively. Gray boxes indicate valid locations for the second motif given the position of the first. The "phase" (distance offset) is assumed to be constant over all sequences and is determined by the algorithm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2200674&req=5

Figure 1: Schematic drawing of the model structure. The triangle and rectangle represent the first and second motif respectively. Gray boxes indicate valid locations for the second motif given the position of the first. The "phase" (distance offset) is assumed to be constant over all sequences and is determined by the algorithm.
Mentions: We propose a de novo method for motif discovery, HeliCis, which can find motif pairs separated by a distance (gap) that varies in a periodical manner. More specifically, the distance is modeled as some fixed offset φ (the phase) plus a variable integer multiple of the period T (Figure 1). Small deviations from exact periodic spacing may optionally be allowed. HeliCis detects patterns which are common to a group of sequences. A typical input would be regulatory DNA from a set of assumedly coregulated genes. The motif pair is assumed to be either present or absent in each sequence and may optionally be allowed to occur on either strand. The period T is specified by the user, but the program can be provided with a range of periods to evaluate. Upper and lower boundaries for the distance can be specified. The distance can be allowed to be negative, making it possible to find unordered motif pairs. Our method is not limited to finding periodically distributed binding sites. The flexibility of the algorithm makes the task of finding colocalized motifs (e.g. positioned within 100 bp of one another without periodicity) or motifs with fixed spacing (e.g. always exactly 25 bp from each other) into special cases simply achieved by choosing appropriate parameters. E.g. by setting the period to one, the model will find colocalized motifs without periodicity. Examples of parameter settings for different scenarios are available on the HeliCis home page[20]. The software also incorporates the possibility to take advantage of interspecies conservation by favoring motif placement in highly conserved regions.

Bottom Line: We show on simulated data that it can efficiently capture the synergistic effects of colocalization and periodic spacing to improve detection of weak DNA motifs.It provides a simple to use web interface which interactively visualizes the current settings and thereby makes it easy to understand the parameters and the model structure.HeliCis provides simple and efficient de novo discovery of colocalized DNA motif pairs, with or without periodic spacing.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wallenberg Laboratory for Cardiovascular Research, Bruna Stråket 16, Sahlgrenska University Hospital, SE-413 45 Göteborg, SWEDEN. erik.larsson@wlab.gu.se

ABSTRACT

Background: Correct temporal and spatial gene expression during metazoan development relies on combinatorial interactions between different transcription factors. As a consequence, cis-regulatory elements often colocalize in clusters termed cis-regulatory modules. These may have requirements on organizational features such as spacing, order and helical phasing (periodic spacing) between binding sites. Due to the turning of the DNA helix, a small modification of the distance between a pair of sites may sometimes drastically disrupt function, while insertion of a full helical turn of DNA (10-11 bp) between cis elements may cause functionality to be restored. Recently, de novo motif discovery methods which incorporate organizational properties such as colocalization and order preferences have been developed, but there are no tools which incorporate periodic spacing into the model.

Results: We have developed a web based motif discovery tool, HeliCis, which features a flexible model which allows de novo detection of motifs with periodic spacing. Depending on the parameter settings it may also be used for discovering colocalized motifs without periodicity or motifs separated by a fixed gap of known or unknown length. We show on simulated data that it can efficiently capture the synergistic effects of colocalization and periodic spacing to improve detection of weak DNA motifs. It provides a simple to use web interface which interactively visualizes the current settings and thereby makes it easy to understand the parameters and the model structure.

Conclusion: HeliCis provides simple and efficient de novo discovery of colocalized DNA motif pairs, with or without periodic spacing. Our evaluations show that it can detect weak periodic patterns which are not easily discovered using a sequential approach, i.e. first finding the binding sites and second analyzing the properties of their pairwise distances.

Show MeSH
Related in: MedlinePlus