Award

Discovery and annotation of regulatory elements in metazoan genomes.

Description: Transcriptional regulatory elements -- both promoters and enhancers -- contain clusters of transcription factor binding sites. I propose a two-stage strategy for finding and annotating these elements. The first stage is to build a dictionary of transcription factor binding motifs (TFBMs). I have previously demonstrated that a novel motif inference tool (NestedMICA) can recover a significant fraction of fruitfly TFBMs. By refining this strategy and applying it to whole-genome datasets, I in tend to build comprehensive motif dictionaries for several key metazoan genomes. I also plan to find and annotate individual regulatory elements on a genome-wide scale. Since enhancers can occur far from the genes that they regulate, this will require new strategies for predicting these elements and -- where available -- integrating these predictions with functional genomics datasets such as ChIP/chip. The second part of this project will be to develop such tools to the point where they can be used to make good-quality regulatory annotation. The goal is to produce regulatory annotation of quality and utility comparable to the computational annotation of protein-coding genes by Ensembl.
Amount: £624,200
Funding type: grant
Funder scheme: Cellular and Molecular Neuroscience
Start date: 2008-02-01
End date: 2013-01-31
Investigator: Down
Institution: University of Cambridge
Funded outputs count: 10
Funder award ID: 083563
OpenAlex ID: G7033654678
2016 · Kenneth J. Evans, Ni Huang, et al. · Proceedings of the National Academy of Sciences · 90
2013 · Carolina Gemma, Sreeram V Ramagopalan, et al. · Genome biology · 21
2012 · Jamie A. Hackett, Roopsha Sengupta, et al. · Science · 795
2011 · Thomas A. Down, Matias Piipari, et al. · Bioinformatics · 94
2010 · Jing Su, Sarah A. Teichmann, et al. · PLoS Computational Biology · 76
2010 · Vardhman K. Rakyan, Thomas A. Down, et al. · Genome Research · 750
2009 · Paulina Kolasinska-Zwierz, Thomas Down, et al. · Nature Genetics · 671
2008 · Thomas A Down, Vardhman K Rakyan, et al. · Nature Biotechnology · 650
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