\textsc{motifDiverge}: a model for assessing the statistical significance of gene regulatory motif divergence between two DNA sequences

DOI10.4310/SII.2015.V8.N4.A6MaRDI QIDQ1747477zbMATH OpenOpenAlexWikidataFDO

Authors Dennis Kostka, Tara Friedrich, Alisha K. Holloway, Katherine Pollard

Publication date 8 May 2018

Published in Statistics and Its Interface (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1402.0042

zbMATH Keywords

binomialChIP-seqgene regulationmotifregulatory evolutiontranscription factor

Mathematics Subject Classification ID

Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10) Protein sequences, DNA sequences (92D20)

Abstract: Next-generation sequencing technology enables the identification of thousands of gene regulatory sequences in many cell types and organisms. We consider the problem of testing if two such sequences differ in their number of binding site motifs for a given transcription factor (TF) protein. Binding site motifs impart regulatory function by providing TFs the opportunity to bind to genomic elements and thereby affect the expression of nearby genes. Evolutionary changes to such functional DNA are hypothesized to be major contributors to phenotypic diversity within and between species; but despite the importance of TF motifs for gene expression, no method exists to test for motif loss or gain. Assuming that motif counts are Binomially distributed, and allowing for dependencies between motif instances in evolutionarily related sequences, we derive the probability mass function of the difference in motif counts between two nucleotide sequences. We provide a method to numerically estimate this distribution from genomic data and show through simulations that our estimator is accurate. Finally, we introduce the R package { t motifDiverge} that implements our methodology and illustrate its application to gene regulatory enhancers identified by a mouse developmental time course experiment. While this study was motivated by analysis of regulatory motifs, our results can be applied to any problem involving two correlated Bernoulli trials.

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Cited in

(4)

• Distance conservation of transcription regulatory motifs in human promoters
• A stochastic model for the evolution of transcription factor binding site abundance
• motifDiverge
• Sampling motifs on phylogenetic trees

Describes a project that uses

Uses Software

• R

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