Molecular Systems Biology - Dissection of a complex transcriptional response using genome-wide transcriptional modelling

A paper has finally been published based on some of the work I did during my PhD. Really thrilled about it and in a top journal too. Thanks go to Martino for a lot of hard work.

Abstract


Modern genomics technologies generate huge data sets creating a demand for systems level, experimentally verified, analysis techniques. We examined the transcriptional response to DNA damage in a human T cell line (MOLT4) using microarrays. By measuring both mRNA accumulation and degradation over a short time course, we were able to construct a mechanistic model of the transcriptional response. The model predicted three dominant transcriptional activity profiles—an early response controlled by NFkappaB and c-Jun, a delayed response controlled by p53, and a late response related to cell cycle re-entry. The method also identified, with defined confidence limits, the transcriptional targets associated with each activity. Experimental inhibition of NFkappaB, c-Jun and p53 confirmed that target predictions were accurate. Model predictions directly explained 70% of the 200 most significantly upregulated genes in the DNA-damage response. Genome-wide transcriptional modelling (GWTM) requires no prior knowledge of either transcription factors or their targets. GWTM is an economical and effective method for identifying the main transcriptional activators in a complex response and confidently predicting their targets.

Comments

Post a Comment

Popular posts from this blog

A census of amplified and overexpressed human cancer genes : Nature Reviews Cancer

This paper , that I am an author on, was released on 24th December 2009: "Integrated genome-wide screens of DNA copy number and gene expression in human cancers have accelerated the rate of discovery of amplified and overexpressed genes. However, the biological importance of most of the genes identified in such studies remains unclear. In this Analysis, we propose a weight-of-evidence based classification system for identifying individual genes in amplified regions that are selected for during tumour development. In a census of the published literature we have identified 77 genes for which there is good evidence of involvement in the development of human cancer." I spent a huge amount of time on this one but I am still pretty low on the author pecking order. This is for a super high impact journal, "Nature Reviews Cancer" which has a 2008 ISI Impact Factor of 30.762. Also check out the associated website which I put together just before Christmas. Hopefully, this...
Read more

RT @CancerInNorwich: 📢 Join us on Monday at 1pm for the next talk in our virtual seminar series. We will be hearing from Dr Wafa Al-Jamal from @QUBelfast, who will be talking about "Smart Nanomedicimes for Pancreatic Cancer". All are welcome to join via the MS Teams link: https://t.co/4xCYpjGuBZ https://t.co/EGyD4NAgeP

RT @CancerInNorwich: 📢 Join us on Monday at 1pm for the next talk in our virtual seminar series. We will be hearing from Dr Wafa Al-Jamal from @QUBelfast, who will be talking about "Smart Nanomedicimes for Pancreatic Cancer". All are welcome to join via the MS Teams link: https://t.co/4xCYpjGuBZ https://t.co/EGyD4NAgeP — Daniel Brewer (@danbrewer) May 11, 2023 from Twitter https://twitter.com/danbrewer
Read more

An excellent opportunity to join the cancer genetics team as a diagnostic lab bioinformatician in Norwich. Lots of exciting projects to get involved in. Deadline: 30/05/2023. Happy to chat about this role. https://t.co/SltGsxYF6Y https://t.co/zh08bqZFDb

An excellent opportunity to join the cancer genetics team as a diagnostic lab bioinformatician in Norwich. Lots of exciting projects to get involved in. Deadline: 30/05/2023. Happy to chat about this role. https://t.co/SltGsxYF6Y https://t.co/zh08bqZFDb — Daniel Brewer (@danbrewer) May 19, 2023 from Twitter https://twitter.com/danbrewer
Read more