codondnds: codondnds

In im3sanger/dndscv: Poisson-based dN/dS models to quantify natural selection in somatic evolution

codondnds

Description

Function to estimate codon-wise dN/dS values and p-values against neutrality. To generate a valid RefCDS input object for this function, use the buildcodon function. Note that recurrent artefacts or SNP contamination can violate the null model and dominate the list of codons under apparent selection. Be very critical of the results and if suspicious codons appear recurrently mutated consider refining the variant calling (e.g. using a better unmatched normal panel).

Usage

codondnds(
  dndsout,
  refcds,
  min_recurr = 2,
  gene_list = NULL,
  codon_list = NULL,
  theta_option = "conservative",
  syn_drivers = "TP53:T125T",
  method = "NB",
  numbins = 10000
)

Arguments

dndsout	Output object from dndscv.
refcds	RefCDS object annotated with codon-level information using the buildcodon function.
min_recurr	Minimum number of mutations per codon to estimate codon-wise dN/dS ratios. [default=2]
gene_list	List of genes to restrict the p-value and q-value calculations (Restricted Hypothesis Testing). Note that q-values are only valid if the list of genes is decided a priori. [default=NULL, codondnds will be run on all genes in dndsout]
codon_list	List of hotspot codons to restrict the p-value and q-value calculations (Restricted Hypothesis Testing). Note that q-values are only valid if the list of codons is decided a priori. [default=NULL, codondnds will be run on all genes in dndsout]
theta_option	2 options: "mle" (uses the MLE of the negative binomial size parameter) or "conservative" (uses the lower bound of the CI95). Values other than "mle" will lead to the conservative option. [default="conservative"]
syn_drivers	Vector with a list of known synonymous driver mutations to exclude from the background model [default="TP53:T125T"]. See Martincorena et al., Cell, 2017 (PMID:29056346).
method	Overdispersion model: NB = Negative Binomial (Gamma-Poisson), LNP = Poisson-Lognormal (see Hess et al., BiorXiv, 2019). [default="NB"]
numbins	Number of bins to discretise the rvec vector [default=1e4]. This enables fast execution of the LNP model in datasets of arbitrarily any size.

Value

'codondnds' returns a table of recurrently mutated codons and the estimates of the size parameter:

- recurcodons: Table of recurrently mutated codons with codon-wise dN/dS values and p-values

- recurcodons_ext: The same table of recurrently mutated codons, but including additional information on the contribution of different changes within a codon.

- overdisp: Maximum likelihood estimate and CI95

- LL: Log-likelihood of the fit of the overdispersed model (see "method" argument) to all synonymous sites at a codon level.

Author(s)

Inigo Martincorena (Wellcome Sanger Institute)

im3sanger/dndscv documentation built on Oct. 1, 2023, 1:05 p.m.