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Calculate the Adenosine Editing Index (AEI)

Source: R/calc_AEI.R
calc_AEI.Rd

The Adenosine Editing Index describes the magnitude of A-to-I editing in a sample. The index is a weighted average of editing events (G bases) observed at A positions. The vast majority A-to-I editing occurs in ALU elements in the human genome, and these regions have a high A-to-I editing signal compared to other regions such as coding exons. This function will perform pileup at specified repeat regions and return a summary AEI metric.

Usage

calc_AEI(
  bamfiles,
  fasta,
  alu_ranges = NULL,
  txdb = NULL,
  snp_db = NULL,
  param = FilterParam(),
  BPPARAM = SerialParam(),
  verbose = FALSE
)

Arguments

bamfiles

character vector of paths to indexed bam files. If a named character vector is supplied the names will be used in the output.

fasta

fasta filename

alu_ranges

GRanges with regions to query for calculating the AEI, typically ALU repeats.

txdb

A TxDb object, if supplied, will be used to subset the alu_ranges to those found overlapping genes. Alternatively a GRanges object with gene coordinates. If the library_type, specified by FilterParam, is unstranded then the TxDb will be used to correct the strandness relative to the reference and is a required parameter.

snp_db

either a SNPlocs, GPos, or GRanges object. If supplied, will be used to exclude polymorphic positions prior to calculating the AEI. If calc_AEI() will be used many times, one will save time by first identifying SNPs that overlap the supplied alu_ranges, and passing these as a GRanges to snp_db rather than supplying all known SNPs (see get_overlapping_snps()).

param

object of class FilterParam() which specify various filters to apply to reads and sites during pileup.

BPPARAM

A BiocParallelParam object for specifying parallel options for operating over chromosomes.

verbose

report progress on each chromosome?

Value

A named list containing:

  • AEI: a matrix of AEI index values computed for all allelic combinations, one row for each supplied bam file.

  • AEI_per_chrom: a data.frame containing values computed for each chromosome

References

Roth, S.H., Levanon, E.Y. & Eisenberg, E. Genome-wide quantification of ADAR adenosine-to-inosine RNA editing activity. Nat Methods 16, 1131–1138 (2019). https://doi.org/10.1038/s41592-019-0610-9

Examples

suppressPackageStartupMessages(library(Rsamtools))

bamfn <- raer_example("SRR5564269_Aligned.sortedByCoord.out.md.bam")
bam2fn <- raer_example("SRR5564277_Aligned.sortedByCoord.out.md.bam")
bams <- c(bamfn, bam2fn)
names(bams) <- c("ADAR1KO", "WT")

fafn <- raer_example("human.fasta")
mock_alu_ranges <- scanFaIndex(fafn)

res <- calc_AEI(bams, fafn, mock_alu_ranges)
res$AEI
#>                A_C       A_G       A_T       C_A        C_G       C_T       G_A
#> ADAR1KO 0.00927902 0.1019746 0.0278319 0.1237964 0.00000000 0.1100564 0.2364360
#> WT      0.00000000 2.2985864 0.1292293 0.2142033 0.01650982 0.2635046 0.3170769
#>                G_C        G_T       T_A        T_C        T_G
#> ADAR1KO 0.01247194 0.04986909 0.0108272 0.03247456 0.03247456
#> WT      0.00000000 0.00000000 0.0000000 0.01161980 0.01161980