Publications by authors named "Isabel K Darcy"

The emergence of the information age in the last few decades brought with it an explosion of biomedical data. But with great power comes great responsibility: there is now a pressing need for new data analysis algorithms to be developed to make sense of the data and transform this information into knowledge which can be directly translated into the clinic. Topological data analysis (TDA) provides a promising path forward: using tools from the mathematical field of algebraic topology, TDA provides a framework to extract insights into the often high-dimensional, incomplete, and noisy nature of biomedical data.

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An experimental technique called difference topology combined with the mathematics of tangle analysis has been used to unveil the structure of DNA bound by the Mu transpososome. However, difference topology experiments can be difficult and time consuming. We discuss a modification that greatly simplifies this experimental technique.

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Difference topology is an experimental technique that can be used to unveil the topological structure adopted by two or more DNA segments in a stable protein-DNA complex. Difference topology has also been used to detect intermediates in a reaction pathway and to investigate the role of DNA supercoiling. In the present article, we review difference topology as applied to the Mu transpososome.

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Background: Tangle analysis has been applied successfully to study proteins which bind two segments of DNA and can knot and link circular DNA. We show how tangle analysis can be extended to model any stable protein-DNA complex.

Results: We discuss a computational method for finding the topological conformation of DNA bound within a protein complex.

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Unlabelled: TopoICE-R is a three-dimensional visualization and manipulation software for solving 2-string tangle equations and can be used to model the topology of DNA bound by proteins such as recombinases and topoisomerases.

Availability: This software, manual and example files are available at www.knotplot.

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The Flp recombinase of yeast and the Cre recombinase of bacteriophage P1 both belong to the lambda-integrase (Int) family of site-specific recombinases. These recombination systems recognize recombination-target sequences that consist of two 13bp inverted repeats flanking a 6 or 8bp spacer sequence. Recombination reactions involve particular geometric and topological relationships between DNA target sites at synapsis, which we investigate using nicked-circular DNA molecules.

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