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Holmes, I.

Publications and source records attributed to Holmes, I..

2 recordsLinked to original sources

Estimation of Rearrangement Break Rates Across the Genome

Genomic rearrangements provide an important source of novel functions by recombining genes and motifs throughout and between genomes. However, understanding how rearrangement functions to shape genomes is hard because reconstructing rearrangements is a combinatoric problem which often has many solutions. In lieu of reconstructing the history of rearrangements, we answer the question of where rearrangements are occurring in the genome by remaining agnostic to the types of rearrangement and solving the simpler problem of estimating the rate at which double-strand breaks occur at every site in a genome. We phrase this problem in graph theoretic terms and find that it is a special case of the minimum cover problem for an interval graph. We employ and modify existing algorithms for efficiently solving this problem. We implement this method as a Python program, named BRAG, and use it to estimate the break rates in the genome of the model Ascomycete mold, Neurospora crassa. We find evidence that rearrangements are more common in the subtelomeric regions of the chromosomes, which facilitates the evolution of novel genes.

genomics

WTFgenes: What's The Function of these genes? Static sites for model-based gene set analysis

A common technique for interpreting experimentally-identified lists of genes is to look for enrichment of genes associated to particular ontology terms. The most common technique uses the hypergeometric distribution; more recently, a model-based approach was proposed. These approaches must typically be run using downloaded software, or on a server. We develop a collapsed likelihood for model-based gene set analysis and present WTFgenes, an implementation of both hypergeometric and model-based approaches, that can be published as a static site with computation run in JavaScript on the user's web browser client. Apart from hosting files, zero server resources are required: the site can (for example) be served directly from Amazon S3 or GitHub Pages. A C++11 implementation yielding identical results runs roughly twice as fast as the JavaScript version. WTFgenes is available from https://github.com/evoldoers/wtfgenes under the BSD3 license. A demonstration for the Gene Ontology is usable at https://evoldoers.github.io/wtfgo. Contact: Ian Holmes ihholmes+wtfgenes@gmail.com.

bioinformatics