DominoEffect: Identification of significant mutation hotspot residues.

In peterblattmann/DominoEffect: Identification and Annotation of Protein Hotspot Residues

Identification of significant mutation hotspot residues.

Description

The function identifies individual amino acid residues, which accumulate a high fraction of the overall mutation load within a protein. After detecting mutation hotspots, the function obtains UniProt/Swiss-Prot KB functional and structural annotations for the affected protein regions and checks for the sequence agreement.

Usage

  DominoEffect(mutation_dataset, gene_data, snp_data,
min_n_muts = 5, MAF_thresh = 0.01,
flanking_region = c(200, 300),
poisson.thr = 0.01, percentage.thr = 0.15,
ratio.thr = 45, approach = "percentage", write_to_file = "NO",
ens_release = "https://feb2023.archive.ensembl.org")

Arguments

mutation_dataset	Object containing a table with the mutation data (e.g. TCGA point mutations mapped to protein level).
gene_data	DominoData object containing information about Ensembl gene annotations: gene identifiers and regresentative transcript cDNA length.
snp_data	Object containing a table with information on population SNPs.
min_n_muts	Numeric vector defining a minimum number of mutations that need to occur at the same residue. Default: 5
MAF_thresh	Numeric vector that defines Minor allele frequency threshold for considering reported mutations as population SNPs.
flanking_region	Numeric vector that defines size of a window around the mutation that will be considered. Up to two window sizes are allowed.
poisson.thr	Numeric vector that defines a treshold for the adjusted p-value. Residues with an associated p-value that is lower than the defined value are reported. Default: 0.01
percentage.thr	Number defining the fraction of mutations within the window that need to fall on a single residue in order for it to be classified as a hotspot. Default: 0.15
ratio.thr	Number defining a requirement that a number of mutations on a single residue should exceed what would be expected by chance given a background mutation rate in the window (i.e. the surrounding region). Default: 45
approach	Option to define selection criteria to use precentage.thr or ratio.thr as criterion for finding single residue mutation clusters. Options: "both", "percentage" or "ratio". Default = "percentage"
write_to_file	Option if the identified and annotated hotspots should be written to a file (YES or NO). Default: NO
ens_release	Release of ensembl to be used. Default: https://feb2023.archive.ensembl.org

Value

Results table

Author(s)

Marija Buljan <[e-mail]> Peter Blattmann <[e-mail]>

Examples

data("SnpData", package = "DominoEffect")
data("TestData", package = "DominoEffect")
data("DominoData", package = "DominoEffect")

hotspot_mutations <- DominoEffect(mutation_dataset = TestData, 
gene_data = DominoData, snp_data = SnpData)

peterblattmann/DominoEffect documentation built on Nov. 9, 2023, 2:39 a.m.