DOI: 10.1101/498782Dec 20, 2018Paper

A benchmark of computational CRISPR-Cas9 guide design methods

BioRxiv : the Preprint Server for Biology
Jake Bradford, Dimitri Perrin

Abstract

The popularity of CRISPR-based gene editing has resulted in an abundance of tools to design CRISPR-Cas9 guides. This is also driven by the fact that designing highly specific and efficient guides is a crucial, but not trivial, task in using CRISPR for gene editing. Here, we thoroughly analyse the performance of 17 design tools. They are evaluated based on runtime performance, compute requirements, and guides generated. To achieve this, we implemented a method for auditing system resources while a given tool executes, and tested each tool on datasets of increasing size, derived from the mouse genome. We found that only five tools had a computational performance that would allow them to analyse an entire genome in a reasonable time, and without exhausting computing resources. There was wide variation in the guides identified, with some tools reporting every possible guide while others filtered for predicted efficiency. Some tools also failed to exclude guides that would target multiple positions in the genome. We also considered a collection of over a thousand guides for which experimental data is available. For the tools that attempt to filter based on efficiency, 65% to 85% of the guides they reported were experimentally found ...Continue Reading

Related Concepts

Genome
Laboratory mice
Size
Filter - Medical Device
Genome-Wide Association Study
Clustered Regularly Interspaced Short Palindromic Repeats
Gene Editing

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