Run a (limited) Pathway Enrichment Analysis on the results of a Crispr experiment.

Share:

Description

This function enables some limited geneset enrichment-type analysis of data derived from a pooled Crispr screen using the PANTHER pathway database. Specifically, it identifies the set of targets significantly enriched or depleted in a summaryDF object returned from ct.generateResults and compares that set to the remaining targets in the screening library using a hypergeometric test.

Note that many Crispr gRNA libraries specifically target biased sets of genes, often focusing on genes involved in a particular pathway or encoding proteins with a shared biological property. Consequently, the enrichment results returned by this function represent the pathways containing genes disproportionately targeted *within the context of the screen*, and may or may not be informative of the underlying biology in question. This means that pathways not targeted by a Crispr library will obviously never be enriched within the positive target set regardless of their biological relevance, and pathways enriched within a focused library screen are similarly expected to partially reflect the composition of the library and other confounding issues (e.g., number of targets within a pathway). Analysts should therefore use this function with care. For example, it might be unsurprising to detect pathways related to histone modification within a screen employing a crispr library targeting epigenetic regulators.

Usage

1
2
ct.PantherPathwayEnrichment(summaryDF, pvalue.cutoff = 0.01, enrich = TRUE,
  organism = "human", db.cut = 10)

Arguments

summaryDF

A dataframe summarizing the results of the screen, returned by the function ct.generateResults.

pvalue.cutoff

A gene-level p-value cutoff defining targets of interest within the screen. Note that this is a nominal p-value cutoff to preserve end-user flexibility.

enrich

Logical indicating whether to consider guides that are enriched (default) or depleted within the screen.

organism

The species of the cell line used in the screen; currently only 'human' or 'mouse' are supported.

db.cut

Minimum number of genes annotated to a given to a pathway within the screen in order to consider it in the enrichment test.

Value

A dataframe of enriched pathways.

Author(s)

Russell Bainer, Steve Lianoglou

Examples

1
2
data('resultsDF')
ct.PantherPathwayEnrichment(resultsDF, organism = 'mouse')

Want to suggest features or report bugs for rdrr.io? Use the GitHub issue tracker.