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31.05.17 Probing regulation of gene transcription with a computer model

last modified Jun 21, 2017 12:03 PM
Namshik Han from the Kouzarides lab, with Manchester colleagues, presents a computer model for identifying new members of transcription factor networks and new interactions between members.
31.05.17 Probing regulation of gene transcription with a computer model

Fig 3a (extract): Limpet plot to visualise up- and down-regulated genes in wild-type and knock-out mice

TIGERi: modeling and visualizing the responses to perturbation of a transcription factor network

Han N, Noyes HA & Brass A (2017) BMC Bioinformatics Vol 18 (Suppl. 7): 260. DOI: 10.1186/s12859-017-1636-6

 

Abstract from the paper

Background

Transcription factor (TF) networks play a key role in controlling the transfer of genetic information from gene to mRNA. Much progress has been made on understanding and reverse-engineering TF network topologies using a range of experimental and theoretical methodologies. Less work has focused on using these models to examine how TF networks respond to changes in the cellular environment.

Methods

In this paper, we have developed a simple, pragmatic methodology, TIGERi (Transcription-factor-activity Illustrator for Global Explanation of Regulatory interaction), to model the response of an inferred TF network to changes in cellular environment. The methodology was tested using publicly available data comparing gene expression profiles of a mouse p38α (Mapk14) knock-out line to the original wild-type.

Results

Using the model, we have examined changes in the TF network resulting from the presence or absence of p38α. A part of this network was confirmed by experimental work in the original paper. Additional relationships were identified by our analysis, for example between p38α and HNF3, and between p38α and SOX9, and these are strongly supported by published evidence. FXR and MYC were also discovered in our analysis as two novel links of p38α. To provide a computational methodology to the biomedical communities that has more user-friendly interface, we also developed a standalone GUI (graphical user interface) software for TIGERi and it is freely available at https://github.com/namshik/tigeri/.

Conclusions

We therefore believe that our computational approach can identify new members of networks and new interactions between members that are supported by published data but have not been integrated into the existing network models. Moreover, ones who want to analyze their own data with TIGERi could use the software without any command line experience. This work could therefore accelerate researches in transcriptional gene regulation in higher eukaryotes.

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Read more about research in the Kouzarides lab.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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