Kinase substrate scoring

This function generates substrate scores for kinases that pass filtering based on both motifs and dynamic profiles

kinaseSubstrateScore(
  substrate.list,
  mat,
  seqs,
  numMotif = 5,
  numSub = 1,
  species = "mouse",
  verbose = TRUE
)

Arguments

substrate.list

A list of kinases with each element containing an array of substrates.

mat

A matrix with rows correspond to phosphosites and columns correspond to samples.

seqs

An array containing aa sequences surrounding each of all phosphosites. Each sequence has length of 15 (-7, p, +7).

numMotif

Minimum number of sequences used for compiling motif for each kinase. Default is 5.

numSub

Minimum number of phosphosites used for compiling phosphorylation profile for each kinase. Default is 1.

species

Motif list species to be used. Currently there are mouse (default), human and rat.

verbose

Default to TRUE to show messages during the progress. All messages will be suppressed if set to FALSE

Value

A list of 4 elements. motifScoreMatrix, profileScoreMatrix, combinedScoreMatrix, ksActivityMatrix (kinase activity matrix) and their weights.

Examples

data('phospho_L6_ratio_pe')
data('SPSs')
data('PhosphoSitePlus')

ppe <- phospho.L6.ratio.pe
sites = paste(sapply(GeneSymbol(ppe), function(x)x),";",
    sapply(Residue(ppe), function(x)x),
    sapply(Site(ppe), function(x)x),
    ";", sep = "")
grps = gsub("_.+", "", colnames(ppe))
design = model.matrix(~ grps - 1)
ctl = which(sites %in% SPSs)
ppe = RUVphospho(ppe, M = design, k = 3, ctl = ctl)

phosphoL6 = SummarizedExperiment::assay(ppe, "normalised")

# filter for up-regulated phosphosites
phosphoL6.mean <- meanAbundance(phosphoL6, grps = grps)
aov <- matANOVA(mat=phosphoL6, grps = grps)
idx <- (aov < 0.05) & (rowSums(phosphoL6.mean > 0.5) > 0)
phosphoL6.reg <- phosphoL6[idx, ,drop = FALSE]

L6.phos.std <- standardise(phosphoL6.reg)

rownames(L6.phos.std) <- paste0(GeneSymbol(ppe), ";", Residue(ppe), 
    Site(ppe), ";")[idx]

L6.phos.seq <- Sequence(ppe)[idx]

L6.matrices <- kinaseSubstrateScore(PhosphoSite.mouse, L6.phos.std,
    L6.phos.seq, numMotif = 5, numSub = 1)
#> Number of kinases passed motif size filtering: 114
#> Number of kinases passed profile size filtering: 44
#> Scoring phosphosites against kinase motifs:
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#> done.
#> Scoring phosphosites against kinase-substrate profiles:
#> done.
#> Generating combined scores for phosphosites
#> by motifs and phospho profiles:
#> done.