20170329

Goals

We’d like to learn Recurrent mutations in aspects of

• Distribution of the recurrent mutations
  • comparison of missense and nonsense distribution
• relationship with
  • expression level
  • cohorts (or cancer sub types)
• effects
  • in protein protein network

mutation & methylation

BG

• The recurrent nonsense mutations in P53 is at or adjacent to methylation sites.

Does this apply to other recurrent mutations?

Results1

Sequence analysis of p53 mutations

ggplot(data = maf.p53.snp3 ) +
  geom_histogram(aes(x = cdnatype,
                  fill = Variant_Classification),
                  stat = "count")

Ignoring unknown parameters: binwidth, bins, pad

di-nucleotide

ggplot(data=testfind)+geom_histogram(stat="count",aes(x=metpattern,fill=Variant_Classification))

Ignoring unknown parameters: binwidth, bins, pad

Recurrent mutation sites - methylation sites

require(ggplot2)
require(dplyr)
require(ggrepel)
source("../R/plot_pfamdomain.R")
source("../R/pfam_readpfam.R")
source("../R/maf_sumrecur.R")
mshotspots<-c("248","273","175","245","249","282","143","157","220","270","242","175")
recurcut=3
load("../data/tp53test2.rda")
maf.tmp <- maf_sumrecur(testfind)
maf.tmp <-
  maf.tmp %>%
  filter(Variant_Classification %in% c("Nonsense_Mutation"))
maf.tmp$cohort="ALL"
gg <- ggplot(data = maf.tmp %>% filter(recur_bypos > recurcut)) +
    #log
    #  geom_tile(aes(x = Prot_pos, y = cohort, fill = log2(recur_cohort))) +
    #cutoff
    geom_point(aes(
      x = Prot_pos,
      y = cohort,
      color = ifelse(recur_bypos > 10, 10, recur_bypos)
    ),
    size= 3,
    alpha=0.6
    ) +
    geom_segment( inherit.aes = FALSE,
      data=maf.tmp ,
      aes(
       x=Prot_pos,
       xend=Prot_pos,
       y=0,
       yend=Inf),
      colour="red",
      linetype=4,
      alpha=0.02
      )+
    scale_colour_gradient(high = "red", low = "grey") +
    labs(color="Recurrence",fill="Domain")+
#    facet_grid(Variant_Classification ~ .) +
    theme_classic()
    ## add domains
  if(TRUE){
    gg<-gg+plot_pfamdomain("P04637")
  }
  print(gg)