Run a dN/dS analysis on MOBSTER clusters.

This function takes a MOBSTER fit and runs `dndscv` (https://github.com/im3sanger/dndscv) to calculate dN/dS values per cluster. It computes global dN/dS and per gene dN/dS values and makes a plot. dN/dS values are computed with the best fitting MOBSTER model.

dnds(
  x,
  mapping = NULL,
  gene_list = NULL,
  colors = c(Tail = "gray"),
  refdb = "hg19",
  dndscv_plot = c("wall", "wmis", "wnon", "wspl", "wtru"),
  ...
)

Arguments

x	A MOBSTER fit object.
mapping	The groups used to compute this statistics are defined by this variable. If `mapping = c(`A` = 'G1', `B` = 'G1', `C` = 'G2')`, then mutations from clusters `A` and `B` will be pooled into one group (`G1`), while mutations from cluster `C` will constitute a group themselves. By default, with `mapping = NULL`, each cluster is a group.
gene_list	An optional vector of gene names to infer dN/dS values, default (`NULL`) is to use dndscv default (whole-exome. This package provides lists genes that can be used for this value (essential genes, cancer genes, etc.); see package data.
colors	If provided, these colours will be used for each cluster. If a subset of colours is provided, palette Set1 from RColorBrewer is used. By default the tail colour is provided as 'gainsboro'.
refdb	The genome referene to use, default is to use hg19. Other references are available from https://github.com/im3sanger/dndscv_data
dndscv_plot	What of the dndscv scores should be visualized in a plot, by default all the statistcs are reported. One can use `dndscv_plot = wall` to get only the global dnds value.
...	Extra parameters forwarded to dndscv.

Value

The fit object is a list with the summary table and the observation counts reported by package dndscv, together with a ggplot plot for the results.

Examples

# Example run with real data
data('LUFF76_lung_sample', package = 'mobster')

clusters = Clusters(LUFF76_lung_sample$best)

dnds_stats = dnds(clusters, gene_list = NULL)
#> Missing 'sample' column, assuming mutations from a single patient (adding a sample label otherwise).
#> Warning: Unknown or uninitialised column: `sample`.
#> ℹ 2298 mutations; 'by cluster' groups in 0 samples, with no genes (default dndscv).
#> [refdb = hg19] Removing chr from chromosome names for hg19 reference compatability
#> 
#>   C1 Tail 
#> 1222 1076 
#> 
#> ── Running dndscv ──────────────────────────────────────────────────────────────
#> 
#> ── Group Tail 
#> [1] Loading the environment...
#> [2] Annotating the mutations...
#> Warning: Mutations observed in contiguous sites within a sample. Please annotate or remove dinucleotide or complex substitutions for best results.
#> [3] Estimating global rates...
#> Warning: glm.fit: fitted rates numerically 0 occurred
#> Warning: glm.fit: fitted rates numerically 0 occurred
#> Warning: glm.fit: fitted rates numerically 0 occurred
#> [4] Running dNdSloc...
#> [5] Running dNdScv...
#>     Regression model for substitutions (theta = 6.69e-05).
#> 
#> ── Group C1 
#> [1] Loading the environment...
#> [2] Annotating the mutations...
#> Warning: Mutations observed in contiguous sites within a sample. Please annotate or remove dinucleotide or complex substitutions for best results.
#> [3] Estimating global rates...
#> Warning: glm.fit: algorithm did not converge
#> Warning: glm.fit: fitted rates numerically 0 occurred
#> Warning: glm.fit: algorithm did not converge
#> Warning: glm.fit: fitted rates numerically 0 occurred
#> Warning: glm.fit: algorithm did not converge
#> Warning: glm.fit: fitted rates numerically 0 occurred
#> [4] Running dNdSloc...
#> [5] Running dNdScv...
#> dndscv error
#> Error in while ((it <- it + 1) < limit && abs(del) > eps) {: missing value where TRUE/FALSE needed
#> 
#> ── dndscv results ────────────────────────────── wall, wmis, wnon, wspl, wtru ──
#> # A tibble: 5 x 5
#>   name            mle cilow cihigh dnds_group
#>   <chr>         <dbl> <dbl>  <dbl> <chr>     
#> 1 wmis  0.731         0.113   4.73 Tail      
#> 2 wnon  0.00000000804 0     Inf    Tail      
#> 3 wspl  0.0000000260  0     Inf    Tail      
#> 4 wtru  0.0000000170  0     Inf    Tail      
#> 5 wall  0.701         0.109   4.51 Tail