Exact p-value calculation for heterotypic clusters of regulatory motifs and its application in computational annotation of cis-regulatory modules - GREYC amacc Access content directly
Journal Articles Algorithms for Molecular Biology Year : 2007

Exact p-value calculation for heterotypic clusters of regulatory motifs and its application in computational annotation of cis-regulatory modules

Abstract

Background
cis-Regulatory modules (CRMs) of eukaryotic genes often contain multiple binding sites for transcription factors. The phenomenon that binding sites form clusters in CRMs is exploited in many algorithms to locate CRMs in a genome. This gives rise to the problem of calculating the statistical significance of the event that multiple sites, recognized by different factors, would be found simultaneously in a text of a fixed length. The main difficulty comes from overlapping occurrences of motifs. So far, no tools have been developed allowing the computation of p-values for simultaneous occurrences of different motifs which can overlap.
Results
We developed and implemented an algorithm computing the p-value that s different motifs occur respectively k1, ..., ks or more times, possibly overlapping, in a random text. Motifs can be represented with a majority of popular motif models, but in all cases, without indels. Zero or first order Markov chains can be adopted as a model for the random text. The computational tool was tested on the set of cis-regulatory modules involved in D. melanogaster early development, for which there exists an annotation of binding sites for transcription factors. Our test allowed us to correctly identify transcription factors cooperatively/competitively binding to DNA.
Method
The algorithm that precisely computes the probability of simultaneous motif occurrences is inspired by the Aho-Corasick automaton and employs a prefix tree together with a transition function. The algorithm runs with the O(n|Σ|(m|ℋ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFlecsaaa@3762@| + K|σ|K) ∏i ki) time complexity, where n is the length of the text, |Σ| is the alphabet size, m is the maximal motif length, |ℋ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFlecsaaa@3762@| is the total number of words in motifs, K is the order of Markov model, and ki is the number of occurrences of the ith motif.
Conclusion
The primary objective of the program is to assess the likelihood that a given DNA segment is CRM regulated with a known set of regulatory factors. In addition, the program can also be used to select the appropriate threshold for PWM scanning. Another application is assessing similarity of different motifs.
Availability
Project web page, stand-alone version and documentation can be found at http://bioinform.genetika.ru/AhoPro/
Fichier principal
Vignette du fichier
1748-7188-2-13.pdf (448.17 Ko) Télécharger le fichier
1748-7188-2-13-S1.PDF (94.73 Ko) Télécharger le fichier
1748-7188-2-13-S2.PDF (101.93 Ko) Télécharger le fichier
1748-7188-2-13-S3.BMP (556.05 Ko) Télécharger le fichier
1748-7188-2-13.xml (329.37 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Format : Other
Format : Other
Format : Other
Loading...

Dates and versions

hal-00784463 , version 1 (04-02-2013)

Identifiers

Cite

Valentina Boeva, Julien Clément, Mireille Régnier, Mikhail Roytberg, Vsevolod Makeev. Exact p-value calculation for heterotypic clusters of regulatory motifs and its application in computational annotation of cis-regulatory modules. Algorithms for Molecular Biology, 2007, 2 (1), pp.13. ⟨10.1186/1748-7188-2-13⟩. ⟨hal-00784463⟩
240 View
208 Download

Altmetric

Share

Gmail Facebook X LinkedIn More