ccr.geneSummary: Gene level depletion summary

In francescojm/CRISPRcleanR: Unsupervised correction of gene independent cell responses to CRISPR-cas9 targeting

Gene level depletion summary

Description

This function collapses single-guide RNAs (sgRNAs) depletion log fold-changes (logFCs) on a targeted gene basis, by averaging (using the ccr.geneMeanFCs). In addition it computes also a logFC threshold T such that when considering as significantly depleted all the genes with a depletion logFC < T, the false discover rate (FDR) of prior known non-essential genes is below a given threshold (specificed in input). Finally it calls significantly depleted genes according to the computed threshold.\ The significant threshold is computed using the ccr.PrRc_Curve function, employing a reference list of core-fitness essential genes and a list of non-essential genes, assembled from multiple RNAi studies used as classification template by the BAGEL algorithm to call gene depletion significance (included as the built-in objects BAGEL_essential and BAGEL_nonEssential) [1].

Usage

ccr.geneSummary(sgRNA_FCprofile,
                libraryAnnotation,
                FDRth=0.05)

Arguments

sgRNA_FCprofile	A named numerical vector containing the sgRNAs' log fold-changes, with names corresponding to sgRNAs identifiers.
libraryAnnotation	A data frame containing the sgRNA library annotation (with same format of KY_Library_v1.0)
FDRth	The FDR threshold to consider in order to derive the significance threshold (FDR 5% by default)

Value

A data frame with gene symbols as row names and two columns: the first one indicating the gene depletion logFC and the second one including a boolean value specifying if the gene under consideration is significantly depleted at the indicated FDR level.

Author(s)

Francesco Iorio ([e-mail])

References

[1] BAGEL: a computational framework for identifying essential genes from pooled library screens. Traver Hart and Jason Moffat. BMC Bioinformatics, 2016 vol. 17 p. 164.

See Also

KY_Library_v1.0, ccr.geneMeanFCs, ccr.PrRc_Curve, ccr.PrRc_Curve, BAGEL_essential, BAGEL_nonEssential

Examples

    ## loading corrected sgRNAs log fold-changes and segment annotations for
    ## an example cell line (EPLC-272H)
    data(EPLC.272HcorrectedFCs)

    ## loading sgRNA library annotation
    data(KY_Library_v1.0)

    ## storing sgRNA log fold-changes in a named vector
    FCs<-EPLC.272HcorrectedFCs$corrected_logFCs$avgFC
    names(FCs)<-rownames(EPLC.272HcorrectedFCs$corrected_logFCs)

    ## computing gene level log fold-changes
    geneFCs<-ccr.geneSummary(FCs,KY_Library_v1.0)

francescojm/CRISPRcleanR documentation built on April 30, 2023, 5:41 a.m.