Abstract
Transcriptional networks are central to any biological process and changes affecting transcription factors or their binding sites in the genome are a key factor driving evolution. As more organisms are being sequenced, tools are needed to easily predict transcription factor binding sites (TFBS) presence and affinity from mere inspection of genomic sequences. Although many TFBS discovery algorithms exist, tools for using the DNA binding models they generate are relatively scarce and their use is limited among the biologist community by the lack of flexible and user-friendly tools. We have developed a suite of web tools (called Morpheus) based on the proven Position Weight Matrices (PWM) formalism that can be used without any programing skills and incorporates some unique features such as the presence of dependencies between nucleotides positions or the possibility to compute the predicted occupancy of a large regulatory region using a biophysical model. To illustrate the possibilities and simplicity of Morpheus tools in functional and evolutionary analysis, we have analysed the regulatory link between LEAFY, a key plant transcription factor involved in flower development, and its direct target gene APETALA1 during the divergence of Brassicales clade.
Highlights
The binding of transcription factors (TF) to cis elements is a key component of most biological processes
Methods based on Chromatin Immunoprecipitation (ChIP) such as ChIP-Chip [1], ChIP-Seq [2] or ChIP-exo [3] allow the identification of all genomic regions bound by a given TF in one experimental condition and suites as Bedtools [4, 5] offer many tools to manipulate them
Using mPWM, interdependencies are defined as additional 4(d) matrices (d = 2 for dinucleotide dependency, d = 3 for triplets) for any position combination (Example matrix files are provided as S1 Text and S2 Text)
Summary
The binding of transcription factors (TF) to cis elements is a key component of most biological processes. Being able to detect TF binding sites (TFBS) by inspecting genome sequences helps understanding how organisms work and how they evolved. Methods based on Chromatin Immunoprecipitation (ChIP) such as ChIP-Chip [1], ChIP-Seq [2] or ChIP-exo [3] allow the identification of all genomic regions bound by a given TF in one experimental condition and suites as Bedtools [4, 5] offer many tools to manipulate them. To precisely identify the TFBS present in these regions, estimate their affinity, predict binding sites that might be bound in PLOS ONE | DOI:10.1371/journal.pone.0135586. To precisely identify the TFBS present in these regions, estimate their affinity, predict binding sites that might be bound in PLOS ONE | DOI:10.1371/journal.pone.0135586 August 18, 2015
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