Dataset Information

GRiP: a computational tool to simulate transcription factor binding in prokaryotes.

ABSTRACT:

Motivation

Transcription factors (TFs) are proteins that regulate gene activity by binding to specific sites on the DNA. Understanding the way these molecules locate their target site is of great importance in understanding gene regulation. We developed a comprehensive computational model of this process and estimated the model parameters in (N.R.Zabet and B.Adryan, submitted for publication).

Results

GRiP (gene regulation in prokaryotes) is a highly versatile implementation of this model and simulates the search process in a computationally efficient way. This program aims to provide researchers in the field with a flexible and highly customizable simulation framework. Its features include representation of DNA sequence, TFs and the interaction between TFs and the DNA (facilitated diffusion mechanism), or between various TFs (cooperative behaviour). The software will record both information on the dynamics associated with the search process (locations of molecules) and also steady-state results (affinity landscape, occupancy-bias and collision hotspots).

Availability

http://logic.sysbiol.cam.ac.uk/grip, program and source code

SUBMITTER: Zabet NR

PROVIDER: S-EPMC3338021 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GRiP: a computational tool to simulate transcription factor binding in prokaryotes.

Zabet Nicolae Radu NR Adryan Boris B

Bioinformatics (Oxford, England) 20120316 9

<h4>Motivation</h4>Transcription factors (TFs) are proteins that regulate gene activity by binding to specific sites on the DNA. Understanding the way these molecules locate their target site is of great importance in understanding gene regulation. We developed a comprehensive computational model of this process and estimated the model parameters in (N.R.Zabet and B.Adryan, submitted for publication).<h4>Results</h4>GRiP (gene regulation in prokaryotes) is a highly versatile implementation of th ...[more]

PMID: 22426343

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Project description:BACKGROUND:In the human genome, the transcription factors (TFs) and transcription factor-binding sites (TFBSs) network has a great regulatory function in the biological pathways. Such crosstalk might be affected by the single-nucleotide polymorphisms (SNPs), which could create or disrupt a TFBS, leading to either a disease or a phenotypic defect. Many computational resources have been introduced to predict the TFs binding variations due to SNPs inside TFBSs, sTRAP being one of them. METHODS:A literature review was performed and the experimental data for 18 TFBSs located in 12 genes was provided. The sequences of TFBS motifs were extracted using two different strategies; in the size similar with synthetic target sites used in the experimental techniques, and with 60 bp upstream and downstream of the SNPs. The sTRAP (http://trap.molgen.mpg.de/cgi-bin/trap_two_seq_form.cgi) was applied to compute the binding affinity scores of their cognate TFs in the context of reference and mutant sequences of TFBSs. The alternative bioinformatics model used in this study was regulatory analysis of variation in enhancers (RAVEN; http://www.cisreg.ca/cgi-bin/RAVEN/a). The bioinformatics outputs of our study were compared with experimental data, electrophoretic mobility shift assay (EMSA). RESULTS:In 6 out of 18 TFBSs in the following genes COL1A1, Hb ??, TF, FIX, MBL2, NOS2A, the outputs of sTRAP were inconsistent with the results of EMSA. Furthermore, no p value of the difference between the two scores of binding affinity under the wild and mutant conditions of TFBSs was presented. Nor, were any criteria for preference or selection of any of the measurements of different matrices used for the same analysis. CONCLUSION:Our preliminary study indicated some paradoxical results between sTRAP and experimental data. However, to link the data of sTRAP to the biological functions, its optimization via experimental procedures with the integration of expanded data and applying several other bioinformatics tools might be required.

Project description:The ability of bacteria and archaea to modulate metabolic process, defensive response, and pathogenic capabilities depend on their repertoire of genes and capacity to regulate the expression of them. Transcription factors (TFs) have fundamental roles in controlling these processes. TFs are proteins dedicated to favor and/or impede the activity of the RNA polymerase. In prokaryotes these proteins have been grouped into families that can be found in most of the different taxonomic divisions. In this work, the association between the expansion patterns of 111 protein regulatory families was systematically evaluated in 1351 non-redundant prokaryotic genomes. This analysis provides insights into the functional and evolutionary constraints imposed on different classes of regulatory factors in bacterial and archaeal organisms. Based on their distribution, we found a relationship between the contents of some TF families and genome size. For example, nine TF families that represent 43.7% of the complete collection of TFs are closely associated with genome size; i.e., in large genomes, members of these families are also abundant, but when a genome is small, such TF family sizes are decreased. In contrast, almost 102 families (56.3% of the collection) do not exhibit or show only a low correlation with the genome size, suggesting that a large proportion of duplication or gene loss events occur independently of the genome size and that various yet-unexplored questions about the evolution of these TF families remain. In addition, we identified a group of families that have a similar distribution pattern across Bacteria and Archaea, suggesting common functional and probable coevolution processes, and a group of families universally distributed among all the genomes. Finally, a specific association between the TF families and their additional domains was identified, suggesting that the families sense specific signals or make specific protein-protein contacts to achieve the regulatory roles.

Dataset Information

GRiP: a computational tool to simulate transcription factor binding in prokaryotes.

Motivation

Results

Availability

Publications

GRiP: a computational tool to simulate transcription factor binding in prokaryotes.

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