## ----setup, include=FALSE-------------------------------------------
## use collapse for bookdown, to collapse all the source and output
## blocks from one code chunk into a single block
time0 <- Sys.time()
knitr::opts_chunk$set(echo = TRUE, collapse = TRUE)
options(width = 70)
require(BiocStyle)
require(pander)
## https://bookdown.org/yihui/rmarkdown-cookbook/time-chunk.html
all_times <- list() # store the time for each chunk
knitr::knit_hooks$set(time_it = local({
now <- NULL
function(before, options) {
if (before) {
now <<- Sys.time()
} else {
res <- difftime(Sys.time(), now, units = "secs")
all_times[[options$label]] <<- as.double(res)
}
}
}))
knitr::opts_chunk$set(time_it = TRUE)
## ----frelats, eval=TRUE,echo=FALSE, fig.cap="Relationships between the main functions in OncoSimulR."----
knitr::include_graphics("relfunct.png")
## ----firstload------------------------------------------------------
## Load the package
library(OncoSimulR)
## ---- echo=FALSE----------------------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## ----ex-dag-inf-----------------------------------------------------
## For reproducibility
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## Simulate a DAG
g1 <- simOGraph(4, out = "rT")
## Simulate 10 evolutionary trajectories
s1 <- oncoSimulPop(10, allFitnessEffects(g1, drvNames = 1:4),
mc.cores = 2, ## adapt to your hardware
seed = NULL) ## for reproducibility of vignette
## Sample those data uniformly, and add noise
d1 <- samplePop(s1, timeSample = "unif", propError = 0.1)
## You would now run the appropriate inferential method and
## compare observed and true. For example
## require(Oncotree)
## fit1 <- oncotree.fit(d1)
## Now, you'd compare fitted and original. This is well beyond
## the scope of this document (and OncoSimulR itself).
## ----hidden-rng-exochs, echo = FALSE--------------------------------
## set.seed(NULL)
## ----hiddenochs, echo=FALSE-----------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## ----exochs---------------------------------------------------------
## For reproducibility
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## Specify fitness effects.
## Numeric values arbitrary, but set the intermediate genotype en
## route to ui as mildly deleterious so there is a valley.
## As in Ochs and Desai, the ui and uv genotypes
## can never appear.
u <- 0.2; i <- -0.02; vi <- 0.6; ui <- uv <- -Inf
od <- allFitnessEffects(
epistasis = c("u" = u, "u:i" = ui,
"u:v" = uv, "i" = i,
"v:-i" = -Inf, "v:i" = vi))
## For the sake of extending this example, also turn i into a
## mutator gene
odm <- allMutatorEffects(noIntGenes = c("i" = 50))
## How do mutation and fitness look like for each genotype?
evalAllGenotypesFitAndMut(od, odm, addwt = TRUE)
## ----exochsb--------------------------------------------------------
## Set a small initSize, as o.w. unlikely to pass the valley
initS <- 10
## The number of replicates is tiny, for the sake of speed
## of creation of the vignette. Even fewer in Windows, since we run on a single
## core
if(.Platform$OS.type == "windows") {
nruns <- 4
} else {
nruns <- 10
}
od_sim <- oncoSimulPop(nruns, od, muEF = odm,
fixation = c("u", "i, v"), initSize = initS,
model = "McFL",
mu = 1e-4, detectionDrivers = NA,
finalTime = NA,
detectionSize = NA, detectionProb = NA,
onlyCancer = TRUE,
mc.cores = 2, ## adapt to your hardware
seed = NULL) ## for reproducibility
## What is the frequency of each final genotype?
sampledGenotypes(samplePop(od_sim))
## ----hidden-rng-exochs33, echo = FALSE------------------------------
## set.seed(NULL)
## ----hiddenrng0szen, echo=FALSE-------------------------------------
set.seed(7)
RNGkind("L'Ecuyer-CMRG")
## ----exszendro------------------------------------------------------
## For reproducibility
set.seed(7)
RNGkind("L'Ecuyer-CMRG")
## Repeat the following loop for different combinations of whatever
## interests you, such as number of genes, or distribution of the
## c and sd (which affect how rugged the landscape is), or
## reference genotype, or evolutionary model, or stopping criterion,
## or sampling procedure, or ...
## Generate a random fitness landscape, from the Rough Mount
## Fuji model, with g genes, and c ("slope" constant) and
## reference chosen randomly (reference is random by default and
## thus not specified below). Require a minimal number of
## accessible genotypes
g <- 6
c <- runif(1, 1/5, 5)
rl <- rfitness(g, c = c, min_accessible_genotypes = g)
## Plot it if you want; commented here as it takes long for a
## vignette
## plot(rl)
## Obtain landscape measures from MAGELLAN. Export to MAGELLAN and
## call your own copy of MAGELLAN's binary
## to_Magellan(rl, file = "rl1.txt") ## (Commented out here to avoid writing files)
## or use the binary copy provided with OncoSimulR
## see also below.
Magellan_stats(rl) ## (Commented out here to avoid writing files)
## Simulate evolution in that landscape many times (here just 10)
simulrl <- oncoSimulPop(10, allFitnessEffects(genotFitness = rl),
keepPhylog = TRUE, keepEvery = 1,
initSize = 4000,
seed = NULL, ## for reproducibility
mc.cores = 2) ## adapt to your hardware
## Obtain measures of evolutionary predictability
diversityLOD(LOD(simulrl))
diversityPOM(POM(simulrl))
sampledGenotypes(samplePop(simulrl, typeSample = "whole"))
## ----hidden-rng-exszend, echo = FALSE-------------------------------
## set.seed(NULL)
## ----ex-tomlin1-----------------------------------------------------
sd <- 0.1 ## fitness effect of drivers
sm <- 0 ## fitness effect of mutator
nd <- 20 ## number of drivers
nm <- 5 ## number of mutators
mut <- 10 ## mutator effect
fitnessGenesVector <- c(rep(sd, nd), rep(sm, nm))
names(fitnessGenesVector) <- 1:(nd + nm)
mutatorGenesVector <- rep(mut, nm)
names(mutatorGenesVector) <- (nd + 1):(nd + nm)
ft <- allFitnessEffects(noIntGenes = fitnessGenesVector,
drvNames = 1:nd)
mt <- allMutatorEffects(noIntGenes = mutatorGenesVector)
## ----hiddentom, echo=FALSE------------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## ----ex-tomlin2-----------------------------------------------------
## For reproducibility
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
ddr <- 4
st <- oncoSimulPop(4, ft, muEF = mt,
detectionDrivers = ddr,
finalTime = NA,
detectionSize = NA,
detectionProb = NA,
onlyCancer = TRUE,
keepEvery = NA,
mc.cores = 2, ## adapt to your hardware
seed = NULL) ## for reproducibility
## How long did it take to reach cancer?
unlist(lapply(st, function(x) x$FinalTime))
## ----hidden-rng-tom, echo = FALSE-----------------------------------
## set.seed(NULL)
## ----exusagebau-----------------------------------------------------
K <- 4
sp <- 1e-5
sdp <- 0.015
sdplus <- 0.05
sdminus <- 0.1
cnt <- (1 + sdplus)/(1 + sdminus)
prod_cnt <- cnt - 1
bauer <- data.frame(parent = c("Root", rep("D", K)),
child = c("D", paste0("s", 1:K)),
s = c(prod_cnt, rep(sdp, K)),
sh = c(0, rep(sp, K)),
typeDep = "MN")
fbauer <- allFitnessEffects(bauer)
(b1 <- evalAllGenotypes(fbauer, order = FALSE, addwt = TRUE))
## How does the fitness landscape look like?
plot(b1, use_ggrepel = TRUE) ## avoid overlapping labels
## ----hiddenbau, echo=FALSE------------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## ----exusagebau2----------------------------------------------------
## For reproducibility
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
totalpops <- 5
initSize <- 100
sb1 <- oncoSimulPop(totalpops, fbauer, model = "Exp",
initSize = initSize,
onlyCancer = FALSE,
mc.cores = 2, ## adapt to your hardware
seed = NULL) ## for reproducibility
## What proportion of the simulations reach 4x initSize?
sum(summary(sb1)[, "TotalPopSize"] > (4 * initSize))/totalpops
## ----hidden-rng-exbau, echo = FALSE---------------------------------
## set.seed(NULL)
## ----hiddenbau22, echo=FALSE----------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## ----hhhhbbbb22-----------------------------------------------------
totalpops <- 5
initSize <- 100
sb2 <- oncoSimulPop(totalpops, fbauer, model = "Exp",
initSize = initSize,
onlyCancer = TRUE,
detectionSize = 10 * initSize,
mc.cores = 2, ## adapt to your hardware
seed = NULL) ## for reproducibility
## How long did it take to reach cancer?
unlist(lapply(sb2, function(x) x$FinalTime))
## ----hidden-rng-exbau22, echo = FALSE-------------------------------
## set.seed(NULL)
## ----oex1intro------------------------------------------------------
## Order effects involving three genes.
## Genotype "D, M" has different fitness effects
## depending on whether M or D mutated first.
## Ditto for genotype "F, D, M".
## Meaning of specification: X > Y means
## that X is mutated before Y.
o3 <- allFitnessEffects(orderEffects = c(
"F > D > M" = -0.3,
"D > F > M" = 0.4,
"D > M > F" = 0.2,
"D > M" = 0.1,
"M > D" = 0.5))
## With the above specification, let's double check
## the fitness of the possible genotypes
(oeag <- evalAllGenotypes(o3, addwt = TRUE, order = TRUE))
## ----hiddoef, echo=FALSE--------------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## ----exusageoe2-----------------------------------------------------
## For reproducibility
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
totalpops <- 5
soe1 <- oncoSimulPop(totalpops, o3, model = "Exp",
initSize = 500,
onlyCancer = FALSE,
mc.cores = 2, ## adapt to your hardware
seed = NULL) ## for reproducibility
## What proportion of the simulations do not end up extinct?
sum(summary(soe1)[, "TotalPopSize"] > 0)/totalpops
## ----hidden-rng-exoef, echo = FALSE---------------------------------
## set.seed(NULL)
## ----sswm-rfitness-funct--------------------------------------------
## oncoSimul object -> measures of clonal interference
## they are not averaged over time. One value for sampled time
clonal_interf_per_time <- function(x) {
x <- x$pops.by.time
y <- x[, -1, drop = FALSE]
shannon <- apply(y, 1, OncoSimulR:::shannonI)
tot <- rowSums(y)
half_tot <- tot * 0.5
five_p_tot <- tot * 0.05
freq_most_freq <- apply(y/tot, 1, max)
single_more_half <- rowSums(y > half_tot)
## whether more than 1 clone with more than 5% pop.
how_many_gt_5p <- rowSums(y > five_p_tot)
several_gt_5p <- (how_many_gt_5p > 1)
return(cbind(shannon, ## Diversity of clones
freq_most_freq, ## Frequency of the most freq. clone
single_more_half, ## Any clone with a frequency > 50%?
several_gt_5p, ## Are there more than 1 clones with
## frequency > 5%?
how_many_gt_5p ## How many clones are there with
## frequency > 5%
))
}
## ----sswm-rfitness0, eval=FALSE-------------------------------------
# set.seed(1)
# r7b <- rfitness(7, scale = c(1.2, 0, 1))
#
# ## Large pop sizes: clonal interference
# (sr7b <- oncoSimulIndiv(allFitnessEffects(genotFitness = r7b),
# model = "McFL",
# mu = 1e-6,
# onlyCancer = FALSE,
# finalTime = 400,
# initSize = 1e7,
# keepEvery = 4,
# detectionSize = 1e10))
#
# plot(sr7b, show = "genotypes")
#
# colMeans(clonal_interf_per_time(sr7b))
## ----sswm-rfitness, eval=FALSE--------------------------------------
# ## Small pop sizes: a single clone most of the time
# (sr7c <- oncoSimulIndiv(allFitnessEffects(genotFitness = r7b),
# model = "McFL",
# mu = 1e-6,
# onlyCancer = FALSE,
# finalTime = 60000,
# initSize = 1e3,
# keepEvery = 4,
# detectionSize = 1e10))
#
# plot(sr7c, show = "genotypes")
#
# colMeans(clonal_interf_per_time(sr7c))
#
#
#
# ## Even smaller fitness differences, but large pop. sizes
# set.seed(1); r7b2 <- rfitness(7, scale = c(1.05, 0, 1))
#
# (sr7b2 <- oncoSimulIndiv(allFitnessEffects(genotFitness = r7b2),
# model = "McFL",
# mu = 1e-6,
# onlyCancer = FALSE,
# finalTime = 3500,
# initSize = 1e7,
# keepEvery = 4,
# detectionSize = 1e10))
# sr7b2
# plot(sr7b2, show = "genotypes")
# colMeans(clonal_interf_per_time(sr7b2))
#
#
# ## Increase pop size further
# (sr7b3 <- oncoSimulIndiv(allFitnessEffects(genotFitness = r7b2),
# model = "McFL",
# mu = 1e-6,
# onlyCancer = FALSE,
# finalTime = 1500,
# initSize = 1e8,
# keepEvery = 4,
# detectionSize = 1e10))
# sr7b3
# plot(sr7b3, show = "genotypes")
# colMeans(clonal_interf_per_time(sr7b3))
#
## ---- results="hide",message=FALSE, echo=TRUE, include=TRUE---------
library(OncoSimulR)
library(graph)
library(igraph)
igraph_options(vertex.color = "SkyBlue2")
## ---- echo=FALSE, results='hide'----------------------------------
options(width = 68)
## -----------------------------------------------------------------
packageVersion("OncoSimulR")
## ---- fig.width=6.5, fig.height=10--------------------------------
## 1. Fitness effects: here we specify an
## epistatic model with modules.
sa <- 0.1
sb <- -0.2
sab <- 0.25
sac <- -0.1
sbc <- 0.25
sv2 <- allFitnessEffects(epistasis = c("-A : B" = sb,
"A : -B" = sa,
"A : C" = sac,
"A:B" = sab,
"-A:B:C" = sbc),
geneToModule = c(
"A" = "a1, a2",
"B" = "b",
"C" = "c"),
drvNames = c("a1", "a2", "b", "c"))
evalAllGenotypes(sv2, addwt = TRUE)
## 2. Simulate the data. Here we use the "McFL" model and set
## explicitly parameters for mutation rate, initial size, size
## of the population that will end the simulations, etc
RNGkind("Mersenne-Twister")
set.seed(983)
ep1 <- oncoSimulIndiv(sv2, model = "McFL",
mu = 5e-6,
sampleEvery = 0.025,
keepEvery = 0.5,
initSize = 2000,
finalTime = 3000,
onlyCancer = FALSE)
## ----iep1x1,fig.width=6.5, fig.height=4.5, fig.cap="Plot of drivers of an epistasis simulation."----
## 3. We will not analyze those data any further. We will only plot
## them. For the sake of a small plot, we thin the data.
plot(ep1, show = "drivers", xlim = c(0, 1500),
thinData = TRUE, thinData.keep = 0.5)
## ----fepancr1, fig.width=5----------------------------------------
## 1. Fitness effects:
pancr <- allFitnessEffects(
data.frame(parent = c("Root", rep("KRAS", 4),
"SMAD4", "CDNK2A",
"TP53", "TP53", "MLL3"),
child = c("KRAS","SMAD4", "CDNK2A",
"TP53", "MLL3",
rep("PXDN", 3), rep("TGFBR2", 2)),
s = 0.1,
sh = -0.9,
typeDep = "MN"),
drvNames = c("KRAS", "SMAD4", "CDNK2A", "TP53",
"MLL3", "TGFBR2", "PXDN"))
## ----figfpancr1, fig.width=5, fig.cap="Plot of DAG corresponding to fitnessEffects object."----
## Plot the DAG of the fitnessEffects object
plot(pancr)
## ----theformerunnamed6--------------------------------------------
## 2. Simulate from it. We change several possible options.
set.seed(1) ## Fix the seed, so we can repeat it
## We set a small finalTime to speed up the vignette
ep2 <- oncoSimulIndiv(pancr, model = "McFL",
mu = 1e-6,
sampleEvery = 0.02,
keepEvery = 1,
initSize = 1000,
finalTime = 20000,
detectionDrivers = 3,
onlyCancer = FALSE)
## ----iep2x2, fig.width=6.5, fig.height=5, fig.cap= "Plot of genotypes of a simulation from a DAG."----
## 3. What genotypes and drivers we get? And play with limits
## to show only parts of the data. We also aggressively thin
## the data.
par(cex = 0.7)
plot(ep2, show = "genotypes", xlim = c(500, 1800),
ylim = c(0, 2400),
thinData = TRUE, thinData.keep = 0.3)
## -----------------------------------------------------------------
citation("OncoSimulR")
## ----colnames_benchmarks, echo = FALSE, eval = TRUE---------------
data(benchmark_1)
data(benchmark_1_0.05)
data(benchmark_2)
data(benchmark_3)
colnames(benchmark_1)[
match(c(
"time_per_simul",
"size_mb_per_simul", "NumClones.Median", "NumIter.Median",
"FinalTime.Median", "TotalPopSize.Median", "TotalPopSize.Mean",
"TotalPopSize.Max.", "keepEvery", "Attempts.Median",
"Attempts.Mean", "Attempts.Max.",
"PDBaseline", "n2", "onlyCancer"),
colnames(benchmark_1)
)] <- c("Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean",
"Total Population Size, max.",
"keepEvery",
"Attempts until Cancer, median",
"Attempts until Cancer, mean",
"Attempts until Cancer, max.",
"PDBaseline", "n2", "onlyCancer"
)
colnames(benchmark_1_0.05)[
match(c("time_per_simul",
"size_mb_per_simul", "NumClones.Median", "NumIter.Median",
"FinalTime.Median", "TotalPopSize.Median", "TotalPopSize.Mean",
"TotalPopSize.Max.",
"keepEvery",
"PDBaseline", "n2", "onlyCancer", "Attempts.Median"),
colnames(benchmark_1_0.05))] <- c("Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean",
"Total Population Size, max.",
"keepEvery",
"PDBaseline", "n2", "onlyCancer",
"Attempts until Cancer, median"
)
colnames(benchmark_2)[match(c("Model", "fitness", "time_per_simul",
"size_mb_per_simul", "NumClones.Median", "NumIter.Median",
"FinalTime.Median", "TotalPopSize.Median", "TotalPopSize.Mean",
"TotalPopSize.Max."), colnames(benchmark_2))] <- c("Model",
"Fitness",
"Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean",
"Total Population Size, max."
)
colnames(benchmark_3)[match(c("Model", "fitness", "time_per_simul",
"size_mb_per_simul", "NumClones.Median", "NumIter.Median",
"FinalTime.Median", "TotalPopSize.Median", "TotalPopSize.Mean",
"TotalPopSize.Max."), colnames(benchmark_3))] <- c("Model",
"Fitness",
"Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean",
"Total Population Size, max."
)
## ----timing1, eval=FALSE------------------------------------------
# ## Specify fitness
# pancr <- allFitnessEffects(
# data.frame(parent = c("Root", rep("KRAS", 4),
# "SMAD4", "CDNK2A",
# "TP53", "TP53", "MLL3"),
# child = c("KRAS","SMAD4", "CDNK2A",
# "TP53", "MLL3",
# rep("PXDN", 3), rep("TGFBR2", 2)),
# s = 0.1,
# sh = -0.9,
# typeDep = "MN"),
# drvNames = c("KRAS", "SMAD4", "CDNK2A", "TP53",
# "MLL3", "TGFBR2", "PXDN"))
#
# Nindiv <- 100 ## Number of simulations run.
# ## Increase this number to decrease sampling variation
#
# ## keepEvery = 1
# t_exp1 <- system.time(
# exp1 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = "default",
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = 1,
# model = "Exp",
# mc.cores = 1))["elapsed"]/Nindiv
#
#
# t_mc1 <- system.time(
# mc1 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = "default",
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = 1,
# model = "McFL",
# mc.cores = 1))["elapsed"]/Nindiv
#
# ## keepEvery = NA
# t_exp2 <- system.time(
# exp2 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = "default",
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = NA,
# model = "Exp",
# mc.cores = 1))["elapsed"]/Nindiv
#
#
# t_mc2 <- system.time(
# mc2 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = "default",
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = NA,
# model = "McFL",
# mc.cores = 1))["elapsed"]/Nindiv
#
#
## ---- eval=FALSE--------------------------------------------------
# cat("\n\n\n t_exp1 = ", t_exp1, "\n")
# object.size(exp1)/(Nindiv * 1024^2)
# cat("\n\n")
# summary(unlist(lapply(exp1, "[[", "NumClones")))
# summary(unlist(lapply(exp1, "[[", "NumIter")))
# summary(unlist(lapply(exp1, "[[", "FinalTime")))
# summary(unlist(lapply(exp1, "[[", "TotalPopSize")))
## ----bench1, eval=TRUE, echo = FALSE------------------------------
panderOptions('table.split.table', 99999999)
panderOptions('table.split.cells', 900) ## For HTML
## panderOptions('table.split.cells', 8) ## For PDF
set.alignment('right')
panderOptions('round', 2)
panderOptions('big.mark', ',')
panderOptions('digits', 2)
pander(benchmark_1[1:4, c("Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, max.",
"keepEvery")],
justify = c('left', rep('right', 8)), ## o.w. hlines not right
## caption = "\\label{tab:bench1}Benchmarks of Exp and McFL models using the default `detectionProb` with two settings of `keepEvery`."
)
## ----timing2, eval = FALSE----------------------------------------
# t_exp3 <- system.time(
# exp3 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = c(PDBaseline = 5e4,
# p2 = 0.1, n2 = 5e5,
# checkSizePEvery = 20),
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = 1,
# model = "Exp",
# mc.cores = 1))["elapsed"]/Nindiv
#
# t_exp4 <- system.time(
# exp4 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = c(PDBaseline = 5e4,
# p2 = 0.1, n2 = 5e5,
# checkSizePEvery = 20),
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = NA,
# model = "Exp",
# mc.cores = 1))["elapsed"]/Nindiv
#
#
#
# t_exp5 <- system.time(
# exp5 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = c(PDBaseline = 5e5,
# p2 = 0.1, n2 = 5e7),
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = 1,
# model = "Exp",
# mc.cores = 1))["elapsed"]/Nindiv
#
# t_exp6 <- system.time(
# exp6 <- oncoSimulPop(Nindiv, pancr,
# detectionProb = c(PDBaseline = 5e5,
# p2 = 0.1, n2 = 5e7),
# detectionSize = NA,
# detectionDrivers = NA,
# finalTime = NA,
# keepEvery = NA,
# model = "Exp",
# mc.cores = 1))["elapsed"]/Nindiv
#
## ----bench1b, eval=TRUE, echo = FALSE-----------------------------
panderOptions('table.split.table', 99999999)
panderOptions('table.split.cells', 900) ## For HTML
## panderOptions('table.split.cells', 8) ## For PDF
set.alignment('right')
panderOptions('round', 2)
panderOptions('big.mark', ',')
panderOptions('digits', 2)
pander(benchmark_1[5:8, c("Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, max.",
"keepEvery",
"PDBaseline",
"n2")],
justify = c('left', rep('right', 10)), ## o.w. hlines not right
## round = c(rep(2, 3), rep(0, 7)),
## digits = c(rep(2, 3), rep(1, 7)),
## caption = "\\label{tab:bench1b}Benchmarks of Exp and McFL models modifying the default `detectionProb` with two settings of `keepEvery`."
)
## ----bench1c, eval=TRUE, echo = FALSE-----------------------------
panderOptions('table.split.table', 99999999)
panderOptions('table.split.cells', 900) ## For HTML
## panderOptions('table.split.cells', 12) ## For PDF
set.alignment('right')
panderOptions('round', 2)
panderOptions('big.mark', ',')
panderOptions('digits', 2)
pander(benchmark_1[1:8, c(
"Attempts until Cancer, median",
"Attempts until Cancer, mean",
"Attempts until Cancer, max.",
"PDBaseline",
"n2")],
justify = c('left', rep('right', 5)), ## o.w. hlines not right
## round = c(rep(2, 3), rep(0, 7)),
## digits = c(rep(2, 3), rep(1, 7)),
## caption = "\\label{tab:bench1c}Number of attempts until cancer."
)
## ## data(benchmark_1)
## knitr::kable(benchmark_1[1:8, c("Attempts.Median",
## "PDBaseline", "n2"), drop = FALSE],
## booktabs = TRUE,
## row.names = TRUE,
## col.names = c("Attempts until cancer", "PDBaseline", "n2"),
## caption = "Median number of attempts until cancer.",
## align = "r")
## ----bench1d, eval=TRUE, echo = FALSE-----------------------------
panderOptions('table.split.table', 99999999)
panderOptions('table.split.cells', 900) ## For HTML
## panderOptions('table.split.cells', 8) ## For PDF
panderOptions('table.split.cells', 15) ## does not fit otherwise
set.alignment('right')
panderOptions('round', 3)
pander(benchmark_1[9:16,
c("Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean",
"Total Population Size, max.",
"keepEvery",
"PDBaseline",
"n2")],
justify = c('left', rep('right', 11)), ## o.w. hlines not right
## caption = "\\label{tab:timing3} Benchmarks of models in Table \\@ref(tab:bench1) and \\@ref(tab:bench1b) when run with `onlyCancer = FALSE`."
)
## ----bench1dx0, eval=TRUE, echo = FALSE---------------------------
panderOptions('table.split.table', 99999999)
## panderOptions('table.split.cells', 900) ## For HTML
panderOptions('table.split.cells', 19)
set.alignment('right')
panderOptions('round', 3)
pander(benchmark_1[ , c("Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median", "Total Population Size, median",
"Total Population Size, mean", "Total Population Size, max.",
"keepEvery", "PDBaseline", "n2", "onlyCancer")],
justify = c('left', rep('right', 12)), ## o.w. hlines not right
## caption = "\\label{tab:allr1bck}Benchmarks of all models in Tables \\@ref(tab:bench1), \\@ref(tab:bench1b), and \\@ref(tab:timing3)."
)
## ----bench1dx, eval=TRUE, echo = FALSE----------------------------
## data(benchmark_1_0.05)
## knitr::kable(benchmark_1_0.05[, c("time_per_simul",
## "size_mb_per_simul", "NumClones.Median", "NumIter.Median",
## "FinalTime.Median", "TotalPopSize.Median", "TotalPopSize.Mean",
## "TotalPopSize.Max.",
## "keepEvery",
## "PDBaseline", "n2", "onlyCancer")],
## booktabs = TRUE,
## col.names = c("Elapsed Time, average per simulation (s)",
## "Object Size, average per simulation (MB)",
## "Number of Clones, median",
## "Number of Iterations, median",
## "Final Time, median",
## "Total Population Size, median",
## "Total Population Size, mean",
## "Total Population Size, max.",
## "keepEvery",
## "PDBaseline", "n2", "onlyCancer"
## ),
## ## caption = "Benchmarks of models in Table \@ref(tab:bench1) and
## ## \@ref(tab:bench1b) when run with `onlyCancer = FALSE`",
## align = "c")
panderOptions('table.split.table', 99999999)
## panderOptions('table.split.cells', 900) ## For HTML
panderOptions('table.split.cells', 19)
set.alignment('right')
panderOptions('round', 3)
pander(benchmark_1_0.05[ , c("Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean", "Total Population Size, max.",
"keepEvery", "PDBaseline", "n2", "onlyCancer")],
justify = c('left', rep('right', 12)), ## o.w. hlines not right
## caption = "\\label{tab:timing3xf}Benchmarks of all models in Table \\@ref(tab:allr1bck) using $s=0.05$ (instead of $s=0.1$)."
)
## ----fitusualb, echo = TRUE, eval = FALSE-------------------------
# pancr <- allFitnessEffects(
# data.frame(parent = c("Root", rep("KRAS", 4),
# "SMAD4", "CDNK2A",
# "TP53", "TP53", "MLL3"),
# child = c("KRAS","SMAD4", "CDNK2A",
# "TP53", "MLL3",
# rep("PXDN", 3), rep("TGFBR2", 2)),
# s = 0.1,
# sh = -0.9,
# typeDep = "MN"),
# drvNames = c("KRAS", "SMAD4", "CDNK2A", "TP53",
# "MLL3", "TGFBR2", "PXDN"))
#
#
# ## Random fitness landscape with 6 genes
# ## At least 50 accessible genotypes
# rfl6 <- rfitness(6, min_accessible_genotypes = 50)
# attributes(rfl6)$accessible_genotypes ## How many accessible
# rf6 <- allFitnessEffects(genotFitness = rfl6)
#
#
# ## Random fitness landscape with 12 genes
# ## At least 200 accessible genotypes
# rfl12 <- rfitness(12, min_accessible_genotypes = 200)
# attributes(rfl12)$accessible_genotypes ## How many accessible
# rf12 <- allFitnessEffects(genotFitness = rfl12)
#
#
#
#
# ## Independent genes; positive fitness from exponential distribution
# ## with mean around 0.1, and negative from exponential with mean
# ## around -0.02. Half of genes positive fitness effects, half
# ## negative.
#
# ng <- 200 re_200 <- allFitnessEffects(noIntGenes = c(rexp(ng/2, 10),
# -rexp(ng/2, 50)))
#
# ng <- 500
# re_500 <- allFitnessEffects(noIntGenes = c(rexp(ng/2, 10),
# -rexp(ng/2, 50)))
#
# ng <- 2000
# re_2000 <- allFitnessEffects(noIntGenes = c(rexp(ng/2, 10),
# -rexp(ng/2, 50)))
#
# ng <- 4000
# re_4000 <- allFitnessEffects(noIntGenes = c(rexp(ng/2, 10),
# -rexp(ng/2, 50)))
#
## ----exp-usual-r, eval = FALSE, echo = TRUE-----------------------
#
# oncoSimulPop(Nindiv,
# fitness,
# detectionProb = NA,
# detectionSize = 1e6,
# initSize = 500,
# detectionDrivers = NA,
# keepPhylog = TRUE,
# model = "Exp",
# errorHitWallTime = FALSE,
# errorHitMaxTries = FALSE,
# finalTime = 5000,
# onlyCancer = FALSE,
# mc.cores = 1,
# sampleEvery = 0.5,
# keepEvery = 1)
## ----mc-usual-r, eval = FALSE, echo = TRUE------------------------
# initSize <- 1000
# oncoSimulPop(Nindiv,
# fitness,
# detectionProb = c(
# PDBaseline = 1.4 * initSize,
# n2 = 2 * initSize,
# p2 = 0.1,
# checkSizePEvery = 4),
# initSize = initSize,
# detectionSize = NA,
# detectionDrivers = NA,
# keepPhylog = TRUE,
# model = "McFL",
# errorHitWallTime = FALSE,
# errorHitMaxTries = FALSE,
# finalTime = 5000,
# max.wall.time = 10,
# onlyCancer = FALSE,
# mc.cores = 1,
# keepEvery = 1)
#
## ----benchustable, eval=TRUE, echo = FALSE------------------------
## data(benchmark_2)
## knitr::kable(benchmark_2[, c("Model", "fitness", "time_per_simul",
## "size_mb_per_simul", "NumClones.Median", "NumIter.Median",
## "FinalTime.Median", "TotalPopSize.Median", "TotalPopSize.Mean",
## "TotalPopSize.Max.")],
## booktabs = TRUE,
## col.names = c("Model",
## "Fitness",
## "Elapsed Time, average per simulation (s)",
## "Object Size, average per simulation (MB)",
## "Number of Clones, median",
## "Number of Iterations, median",
## "Final Time, median",
## "Total Population Size, median",
## "Total Population Size, mean",
## "Total Population Size, max."
## ),
## align = "c")
panderOptions('table.split.table', 99999999)
panderOptions('table.split.cells', 900) ## For HTML
## panderOptions('table.split.cells', 8) ## For PDF
## set.alignment('right', row.names = 'center')
panderOptions('table.alignment.default', 'right')
panderOptions('round', 3)
pander(benchmark_2[ , c(
"Model", "Fitness",
"Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean",
"Total Population Size, max.")],
justify = c('left', 'left', rep('right', 8)),
## caption = "\\label{tab:timingusual}Benchmarks under some common use cases, set 1."
)
## ----benchustable2, eval=TRUE, echo = FALSE-----------------------
## data(benchmark_3)
## knitr::kable(benchmark_3[, c("Model", "fitness", "time_per_simul",
## "size_mb_per_simul", "NumClones.Median", "NumIter.Median",
## "FinalTime.Median", "TotalPopSize.Median", "TotalPopSize.Mean",
## "TotalPopSize.Max.")],
## booktabs = TRUE,
## col.names = c("Model",
## "Fitness", "Elapsed Time, average per simulation (s)",
## "Object Size, average per simulation (MB)",
## "Number of Clones, median",
## "Number of Iterations, median",
## "Final Time, median",
## "Total Population Size, median",
## "Total Population Size, mean",
## "Total Population Size, max."
## ),
## align = "c")
panderOptions('table.split.table', 99999999)
panderOptions('table.split.cells', 900) ## For HTML
## panderOptions('table.split.cells', 8) ## For PDF
panderOptions('round', 3)
panderOptions('table.alignment.default', 'right')
pander(benchmark_3[ , c(
"Model", "Fitness",
"Elapsed Time, average per simulation (s)",
"Object Size, average per simulation (MB)",
"Number of Clones, median",
"Number of Iterations, median",
"Final Time, median",
"Total Population Size, median",
"Total Population Size, mean",
"Total Population Size, max.")],
justify = c('left', 'left', rep('right', 8)),
## caption = "\\label{tab:timingusual2}Benchmarks under some common use cases, set 2."
)
## ----exp10000, echo = TRUE, eval = FALSE--------------------------
# ng <- 10000
# u <- allFitnessEffects(noIntGenes = c(rep(0.1, ng/2),
# rep(-0.1, ng/2)))
#
# t_e_10000 <- system.time(
# e_10000 <- oncoSimulPop(5, u, model = "Exp", mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# mutationPropGrowth = TRUE,
# mc.cores = 1))
## ----exp10000-out, echo = TRUE, eval = FALSE----------------------
# t_e_10000
# ## user system elapsed
# ## 4.368 0.196 4.566
#
# summary(e_10000)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 5017 1180528 415116 143 7547
# ## 2 3726 1052061 603612 131 5746
# ## 3 4532 1100721 259510 132 6674
# ## 4 4150 1283115 829728 99 6646
# ## 5 4430 1139185 545958 146 6748
#
# print(object.size(e_10000), units = "MB")
# ## 863.9 Mb
#
## ----exp10000b, eval = FALSE, echo = TRUE-------------------------
# t_e_10000b <- system.time(
# e_10000b <- oncoSimulPop(5,
# u,
# model = "Exp",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = TRUE,
# mc.cores = 1
# ))
#
## ----exp10000b-out, echo = TRUE, eval = FALSE---------------------
# t_e_10000b
# ## user system elapsed
# ## 5.484 0.100 5.585
#
# summary(e_10000b)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 2465 1305094 727989 91 6447
# ## 2 2362 1070225 400329 204 8345
# ## 3 2530 1121164 436721 135 8697
# ## 4 2593 1206293 664494 125 8149
# ## 5 2655 1186994 327835 191 8572
#
# print(object.size(e_10000b), units = "MB")
# ## 488.3 Mb
#
## ----exp50000, echo = TRUE, eval = FALSE--------------------------
# ng <- 50000
# u <- allFitnessEffects(noIntGenes = c(rep(0.1, ng/2),
# rep(-0.1, ng/2)))
# t_e_50000 <- system.time(
# e_50000 <- oncoSimulPop(5,
# u,
# model = "Exp",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
#
#
# t_e_50000
# ## user system elapsed
# ## 44.192 1.684 45.891
#
# summary(e_50000)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 7367 1009949 335455 75.00 18214
# ## 2 8123 1302324 488469 63.65 17379
# ## 3 8408 1127261 270690 72.57 21144
# ## 4 8274 1138513 318152 80.59 20994
# ## 5 7520 1073131 690814 70.00 18569
#
# print(object.size(e_50000), units = "MB")
# ## 7598.6 Mb
## ----exp50000np, echo = TRUE, eval = FALSE------------------------
# ng <- 50000
# u <- allFitnessEffects(noIntGenes = c(rep(0.1, ng/2),
# rep(-0.1, ng/2)))
# t_e_50000np <- system.time(
# e_50000np <- oncoSimulPop(5,
# u,
# model = "Exp",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = 1,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
#
# t_e_50000np
# ## user system elapsed
# ## 42.316 2.764 45.079
#
# summary(e_50000np)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 13406 1027949 410074 71.97 19469
# ## 2 12469 1071325 291852 66.00 17834
# ## 3 11821 1089834 245720 90.00 16711
# ## 4 14008 1165168 505607 77.61 19675
# ## 5 14759 1074621 205954 87.68 20597
#
# print(object.size(e_50000np), units = "MB")
# ## 12748.4 Mb
#
## ----exp50000mpg, echo = TRUE, eval = FALSE-----------------------
#
# ng <- 50000
# u <- allFitnessEffects(noIntGenes = c(rep(0.1, ng/2),
# rep(-0.1, ng/2)))
#
# t_e_50000c <- system.time(
# e_50000c <- oncoSimulPop(5,
# u,
# model = "Exp",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = TRUE,
# mc.cores = 1
# ))
#
# t_e_50000c
# ## user system elapsed
# ## 84.228 2.416 86.665
#
# summary(e_50000c)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 11178 1241970 344479 84.74 27137
# ## 2 12820 1307086 203544 91.94 33448
# ## 3 10592 1126091 161057 83.81 26064
# ## 4 11883 1351114 148986 65.68 25396
# ## 5 10518 1101392 253523 99.79 26082
#
# print(object.size(e_50000c), units = "MB")
# ## 10904.9 Mb
#
## ----sizedetail, eval = FALSE, echo = TRUE------------------------
# r1 <- oncoSimulIndiv(u,
# model = "Exp",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# mutationPropGrowth = TRUE
# )
# summary(r1)[c(1, 8)]
# ## NumClones FinalTime
# ## 1 3887 345
#
# print(object.size(r1), units = "MB")
# ## 160 Mb
#
# ## Size of the two largest objects inside:
# sizes <- lapply(r1, function(x) object.size(x)/(1024^2))
# sort(unlist(sizes), decreasing = TRUE)[1:2]
# ## Genotypes pops.by.time
# ## 148.28 10.26
#
# dim(r1$Genotypes)
# ## [1] 10000 3887
## ----mc50000_1, echo = TRUE, eval = FALSE-------------------------
# ng <- 50000
# u <- allFitnessEffects(noIntGenes = c(rep(0.1, ng/2),
# rep(-0.1, ng/2)))
#
# t_mc_50000_nmpg <- system.time(
# mc_50000_nmpg <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
# t_mc_50000_nmpg
# ## user system elapsed
# ## 30.46 0.54 31.01
#
#
# summary(mc_50000_nmpg)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 1902 1002528 582752 284.2 31137
# ## 2 2159 1002679 404858 274.8 36905
# ## 3 2247 1002722 185678 334.5 42429
# ## 4 2038 1009606 493574 218.4 32519
# ## 5 2222 1004661 162628 291.0 38470
#
# print(object.size(mc_50000_nmpg), units = "MB")
# ## 2057.6 Mb
#
## ----mc50000_kp, echo = TRUE, eval = FALSE------------------------
# t_mc_50000_nmpg_k <- system.time(
# mc_50000_nmpg_k <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = 1,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
#
# t_mc_50000_nmpg_k
# ## user system elapsed
# ## 30.000 1.712 31.714
#
# summary(mc_50000_nmpg_k)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 8779 1000223 136453 306.7 38102
# ## 2 7442 1006563 428150 345.3 35139
# ## 3 8710 1003509 224543 252.3 35659
# ## 4 8554 1002537 103889 273.7 36783
# ## 5 8233 1003171 263005 301.8 35236
#
# print(object.size(mc_50000_nmpg_k), units = "MB")
# ## 8101.4 Mb
## ----mc50000_popx, echo = TRUE, eval = FALSE----------------------
# ng <- 50000
# u <- allFitnessEffects(noIntGenes = c(rep(0.1, ng/2),
# rep(-0.1, ng/2)))
#
# t_mc_50000_nmpg_3e6 <- system.time(
# mc_50000_nmpg_3e6 <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 1e-7,
# detectionSize = 3e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
# t_mc_50000_nmpg_3e6
# ## user system elapsed
# ## 77.240 1.064 78.308
#
# summary(mc_50000_nmpg_3e6)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 5487 3019083 836793 304.5 65121
# ## 2 4812 3011816 789146 286.3 53087
# ## 3 4463 3016896 1970957 236.6 45918
# ## 4 5045 3028142 956026 360.3 63464
# ## 5 4791 3029720 916692 358.1 55012
#
# print(object.size(mc_50000_nmpg_3e6), units = "MB")
# ## 4759.3 Mb
#
## ----mc50000_mux, echo = TRUE, eval = FALSE-----------------------
#
# t_mc_50000_nmpg_5mu <- system.time(
# mc_50000_nmpg_5mu <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 5e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
#
# t_mc_50000_nmpg_5mu
# ## user system elapsed
# ## 167.332 1.796 169.167
#
# summary(mc_50000_nmpg_5mu)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 7963 1004415 408352 99.03 57548
# ## 2 8905 1010751 120155 130.30 74738
# ## 3 8194 1005465 274661 96.98 58546
# ## 4 9053 1014049 119943 112.23 75379
# ## 5 8982 1011817 95047 99.95 76757
#
# print(object.size(mc_50000_nmpg_5mu), units = "MB")
# ## 8314.4 Mb
## ----mcf5muk, echo = TRUE, eval = FALSE---------------------------
# t_mc_50000_nmpg_5mu_k <- system.time(
# mc_50000_nmpg_5mu_k <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 5e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = 1,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
#
# t_mc_50000_nmpg_5mu_k
# ## user system elapsed
# ## 174.404 5.068 179.481
#
# summary(mc_50000_nmpg_5mu_k)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 25294 1001597 102766 123.4 74524
# ## 2 23766 1006679 223010 124.3 71808
# ## 3 21755 1001379 203638 114.8 62609
# ## 4 24889 1012103 161003 119.3 75031
# ## 5 21844 1002927 255388 108.8 64556
#
# print(object.size(mc_50000_nmpg_5mu_k), units = "MB")
# ## 22645.8 Mb
#
## ----mc50000_2, echo = TRUE, eval = FALSE-------------------------
#
# t_mc_50000 <- system.time(
# mc_50000 <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = TRUE,
# mc.cores = 1
# ))
#
# t_mc_50000
# ## user system elapsed
# ## 303.352 2.808 306.223
#
# summary(mc_50000)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 13928 1010815 219814 210.9 91255
# ## 2 12243 1003267 214189 178.1 67673
# ## 3 13880 1014131 124354 161.4 88322
# ## 4 14104 1012941 75521 205.7 98583
# ## 5 12428 1005594 232603 167.4 70359
#
# print(object.size(mc_50000), units = "MB")
# ## 12816.6 Mb
#
## ----mcf5muk005, echo = TRUE, eval = FALSE------------------------
# t_mc_50000_nmpg_5mu_k <- system.time(
# mc_50000_nmpg_5mu_k <- oncoSimulPop(2,
# u,
# model = "McFL",
# mu = 5e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = 1,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
# t_mc_50000_nmpg_5mu_k
# ## user system elapsed
# ## 305.512 5.164 310.711
#
# summary(mc_50000_nmpg_5mu_k)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 61737 1003273 104460 295.8731 204214
# ## 2 65072 1000540 133068 296.6243 210231
#
# print(object.size(mc_50000_nmpg_5mu_k), units = "MB")
# ## 24663.6 Mb
#
## ----mc50000_1_005, echo = TRUE, eval = FALSE---------------------
# t_mc_50000_nmpg <- system.time(
# mc_50000_nmpg <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 1e-7,
# detectionSize = 1e6,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# keepEvery = NA,
# mutationPropGrowth = FALSE,
# mc.cores = 1
# ))
# t_mc_50000_nmpg
# ## user system elapsed
# ## 111.236 0.596 111.834
#
# summary(mc_50000_nmpg)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 2646 1000700 217188 734.475 108566
# ## 2 2581 1001626 209873 806.500 107296
# ## 3 2903 1001409 125148 841.700 120859
# ## 4 2310 1000146 473948 906.300 91519
# ## 5 2704 1001290 448409 838.800 103556
#
# print(object.size(mc_50000_nmpg), units = "MB")
# ## 2638.3 Mb
#
## ----filog_exp50000_1, echo = TRUE, eval = FALSE------------------
# head(e_50000[[1]]$other$PhylogDF)
# ## parent child time
# ## 1 3679 0.8402
# ## 2 4754 1.1815
# ## 3 20617 1.4543
# ## 4 15482 2.3064
# ## 5 4431 3.7130
# ## 6 41915 4.0628
#
# tail(e_50000[[1]]$other$PhylogDF)
# ## parent child time
# ## 20672 3679, 20282 3679, 20282, 22359 75.0
# ## 20673 3679, 17922, 22346 3679, 17922, 22346, 35811 75.0
# ## 20674 2142, 3679 2142, 3679, 25838 75.0
# ## 20675 3679, 17922, 19561 3679, 17922, 19561, 43777 75.0
# ## 20676 3679, 15928, 19190, 20282 3679, 15928, 19190, 20282, 49686 75.0
# ## 20677 2142, 3679, 16275 2142, 3679, 16275, 24201 75.0
## ----noplotlconephylog, echo = TRUE, eval = FALSE-----------------
# plotClonePhylog(e_50000[[1]]) ## plot not shown
#
## ----ex-large-pop-size, eval = FALSE, echo = TRUE-----------------
# ng <- 50
# u <- allFitnessEffects(noIntGenes = c(rep(0.1, ng)))
## ----ex-large-mf, eval = FALSE, echo = TRUE-----------------------
# t_mc_k_50_1e11 <- system.time(
# mc_k_50_1e11 <- oncoSimulPop(5,
# u,
# model = "McFL",
# mu = 1e-7,
# detectionSize = 1e11,
# initSize = 1e5,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# mutationPropGrowth = FALSE,
# keepEvery = 1,
# finalTime = 5000,
# mc.cores = 1,
# max.wall.time = 600
# ))
#
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
#
# t_mc_k_50_1e11
# ## user system elapsed
# ## 613.612 0.040 613.664
#
# summary(mc_k_50_1e11)[, c(1:3, 8, 9)]
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 5491 100328847809 44397848771 1019.950 942764
# ## 2 3194 100048090441 34834178374 789.675 888819
# ## 3 5745 100054219162 24412502660 927.950 929231
# ## 4 4017 101641197799 60932177160 750.725 480938
# ## 5 5393 100168156804 41659212367 846.250 898245
#
# ## print(object.size(mc_k_50_1e11), units = "MB")
# ## 177.8 Mb
#
## ----ex-large-exp, eval = FALSE, echo = TRUE----------------------
# t_exp_k_50_1e11 <- system.time(
# exp_k_50_1e11 <- oncoSimulPop(5,
# u,
# model = "Exp",
# mu = 1e-7,
# detectionSize = 1e11,
# initSize = 1e5,
# detectionDrivers = NA,
# detectionProb = NA,
# keepPhylog = TRUE,
# onlyCancer = FALSE,
# mutationPropGrowth = FALSE,
# keepEvery = 1,
# finalTime = 5000,
# mc.cores = 1,
# max.wall.time = 600,
# errorHitWallTime = FALSE,
# errorHitMaxTries = FALSE
# ))
#
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Hitted wall time. Exiting.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Hitted wall time. Exiting.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Recoverable exception ti set to DBL_MIN. Rerunning.
# ## Hitted wall time. Exiting.
# ## Hitted wall time. Exiting.
#
# t_exp_k_50_1e11
# ## user system elapsed
# ## 2959.068 0.128 2959.556
# try(summary(exp_k_50_1e11)[, c(1:3, 8, 9)])
# ## NumClones TotalPopSize LargestClone FinalTime NumIter
# ## 1 6078 65172752616 16529682757 235.7590 1883438
# ## 2 5370 106476643712 24662446729 232.0000 2516675
# ## 3 2711 21911284363 17945303353 224.8608 543698
# ## 4 2838 13241462284 2944300245 216.8091 372298
# ## 5 7289 76166784312 10941729810 240.0217 1999489
#
# print(object.size(exp_k_50_1e11), units = "MB")
# ## 53.5 Mb
#
## -----------------------------------------------------------------
m4 <- data.frame(G = c("WT", "A", "B", "A, B"), F = c(1, 2, 3, 4))
## -----------------------------------------------------------------
fem4 <- allFitnessEffects(genotFitness = m4)
## -----------------------------------------------------------------
try(plot(fem4))
## ---- fig.width=6.5, fig.height = 6.5-----------------------------
plotFitnessLandscape(evalAllGenotypes(fem4))
## -----------------------------------------------------------------
evalAllGenotypes(fem4, addwt = TRUE)
## -----------------------------------------------------------------
plotFitnessLandscape(evalAllGenotypes(fem4))
## -----------------------------------------------------------------
m6 <- cbind(c(1, 1), c(1, 0), c(2, 3))
fem6 <- allFitnessEffects(genotFitness = m6)
evalAllGenotypes(fem6, addwt = TRUE)
## plot(fem6)
## ---- fig.width=6.5, fig.height = 6.5-----------------------------
plotFitnessLandscape(evalAllGenotypes(fem6))
## ----rj68v3x------------------------------------------------------
r <- data.frame(Genotype = c("WT", "A", "B", "A, B"),
Fitness = c("10 * f_",
"10 * f_1",
"50 * f_2",
"200 * (f_1 + f_2) + 50 * f_1_2"))
afe <- allFitnessEffects(genotFitness = r,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
plotFitnessLandscape(evalAllGenotypes(afe,
spPopSizes = c(WT = 2500, A = 2000,
B = 5500, "A, B" = 700)))
## ----j8hhkiu------------------------------------------------------
r <- data.frame(Genotype = c("WT", "A", "B", "A, B"),
Fitness = c("10 * f_",
"10 * f_A",
"50 * f_B",
"200 * (f_A + f_B) + 50 * f_A_B"))
## ----mcflparam----------------------------------------------------
sp <- 1e-3
spp <- -sp/(1 + sp)
## -----------------------------------------------------------------
ai1 <- evalAllGenotypes(allFitnessEffects(
noIntGenes = c(0.05, -.2, .1)), order = FALSE)
## -----------------------------------------------------------------
ai1
## -----------------------------------------------------------------
all(ai1[, "Fitness"] == c( (1 + .05), (1 - .2), (1 + .1),
(1 + .05) * (1 - .2),
(1 + .05) * (1 + .1),
(1 - .2) * (1 + .1),
(1 + .05) * (1 - .2) * (1 + .1)))
## -----------------------------------------------------------------
(ai2 <- evalAllGenotypes(allFitnessEffects(
noIntGenes = c(0.05, -.2, .1)), order = TRUE,
addwt = TRUE))
## ---- fig.height=4------------------------------------------------
data(examplesFitnessEffects)
plot(examplesFitnessEffects[["cbn1"]])
## -----------------------------------------------------------------
cs <- data.frame(parent = c(rep("Root", 4), "a", "b", "d", "e", "c"),
child = c("a", "b", "d", "e", "c", "c", rep("g", 3)),
s = 0.1,
sh = -0.9,
typeDep = "MN")
cbn1 <- allFitnessEffects(cs)
## ---- fig.height=3------------------------------------------------
plot(cbn1)
## ---- fig.height=5------------------------------------------------
plot(cbn1, "igraph")
## ---- fig.height=5------------------------------------------------
library(igraph) ## to make the reingold.tilford layout available
plot(cbn1, "igraph", layout = layout.reingold.tilford)
## -----------------------------------------------------------------
gfs <- evalAllGenotypes(cbn1, order = FALSE, addwt = TRUE)
gfs[1:15, ]
## -----------------------------------------------------------------
c1 <- data.frame(parent = c(rep("Root", 4), "a", "b", "d", "e", "c"),
child = c("a", "b", "d", "e", "c", "c", rep("g", 3)),
s = c(0.01, 0.02, 0.03, 0.04, 0.1, 0.1, rep(0.2, 3)),
sh = c(rep(0, 4), c(-.1, -.2), c(-.05, -.06, -.07)),
typeDep = "MN")
try(fc1 <- allFitnessEffects(c1))
## -----------------------------------------------------------------
c1 <- data.frame(parent = c(rep("Root", 4), "a", "b", "d", "e", "c"),
child = c("a", "b", "d", "e", "c", "c", rep("g", 3)),
s = c(0.01, 0.02, 0.03, 0.04, 0.1, 0.1, rep(0.2, 3)),
sh = c(rep(0, 4), c(-.9, -.9), rep(-.95, 3)),
typeDep = "MN")
cbn2 <- allFitnessEffects(c1)
## -----------------------------------------------------------------
gcbn2 <- evalAllGenotypes(cbn2, order = FALSE)
gcbn2[1:10, ]
## -----------------------------------------------------------------
gcbn2o <- evalAllGenotypes(cbn2, order = TRUE, max = 1956)
gcbn2o[1:10, ]
## -----------------------------------------------------------------
all.equal(
gcbn2[c(1:21, 22, 28, 41, 44, 56, 63 ) , "Fitness"],
c(1.01, 1.02, 0.1, 1.03, 1.04, 0.05,
1.01 * c(1.02, 0.1, 1.03, 1.04, 0.05),
1.02 * c(0.10, 1.03, 1.04, 0.05),
0.1 * c(1.03, 1.04, 0.05),
1.03 * c(1.04, 0.05),
1.04 * 0.05,
1.01 * 1.02 * 1.1,
1.01 * 0.1 * 0.05,
1.03 * 1.04 * 0.05,
1.01 * 1.02 * 1.1 * 0.05,
1.03 * 1.04 * 1.2 * 0.1, ## notice this
1.01 * 1.02 * 1.03 * 1.04 * 1.1 * 1.2
))
## -----------------------------------------------------------------
gcbn2[56, ]
all.equal(gcbn2[56, "Fitness"], 1.03 * 1.04 * 1.2 * 0.10)
## -----------------------------------------------------------------
s1 <- data.frame(parent = c(rep("Root", 4), "a", "b", "d", "e", "c"),
child = c("a", "b", "d", "e", "c", "c", rep("g", 3)),
s = c(0.01, 0.02, 0.03, 0.04, 0.1, 0.1, rep(0.2, 3)),
sh = c(rep(0, 4), c(-.9, -.9), rep(-.95, 3)),
typeDep = "SM")
smn1 <- allFitnessEffects(s1)
## ---- fig.height=3------------------------------------------------
plot(smn1)
## -----------------------------------------------------------------
gsmn1 <- evalAllGenotypes(smn1, order = FALSE)
## -----------------------------------------------------------------
gcbn2[c(8, 12, 22), ]
gsmn1[c(8, 12, 22), ]
gcbn2[c(20:21, 28), ]
gsmn1[c(20:21, 28), ]
## -----------------------------------------------------------------
x1 <- data.frame(parent = c(rep("Root", 4), "a", "b", "d", "e", "c"),
child = c("a", "b", "d", "e", "c", "c", rep("g", 3)),
s = c(0.01, 0.02, 0.03, 0.04, 0.1, 0.1, rep(0.2, 3)),
sh = c(rep(0, 4), c(-.9, -.9), rep(-.95, 3)),
typeDep = "XMPN")
xor1 <- allFitnessEffects(x1)
## ---- fig.height=3------------------------------------------------
plot(xor1)
## -----------------------------------------------------------------
gxor1 <- evalAllGenotypes(xor1, order = FALSE)
## -----------------------------------------------------------------
gxor1[c(22, 41), ]
c(1.01 * 1.02 * 0.1, 1.03 * 1.04 * 0.05)
## -----------------------------------------------------------------
gxor1[28, ]
1.01 * 1.1 * 1.2
## -----------------------------------------------------------------
gxor1[44, ]
1.01 * 1.02 * 0.1 * 1.2
## -----------------------------------------------------------------
p3 <- data.frame(
parent = c(rep("Root", 4), "a", "b", "d", "e", "c", "f"),
child = c("a", "b", "d", "e", "c", "c", "f", "f", "g", "g"),
s = c(0.01, 0.02, 0.03, 0.04, 0.1, 0.1, 0.2, 0.2, 0.3, 0.3),
sh = c(rep(0, 4), c(-.9, -.9), c(-.95, -.95), c(-.99, -.99)),
typeDep = c(rep("--", 4),
"XMPN", "XMPN", "MN", "MN", "SM", "SM"))
fp3 <- allFitnessEffects(p3)
## ---- fig.height=3------------------------------------------------
plot(fp3)
## ---- fig.height=6------------------------------------------------
plot(fp3, "igraph", layout.reingold.tilford)
## -----------------------------------------------------------------
gfp3 <- evalAllGenotypes(fp3, order = FALSE)
## -----------------------------------------------------------------
gfp3[c(9, 24, 29, 59, 60, 66, 119, 120, 126, 127), ]
c(1.01 * 1.1, 1.03 * .05, 1.01 * 1.02 * 0.1, 0.1 * 0.05 * 1.3,
1.03 * 1.04 * 1.2, 1.01 * 1.02 * 0.1 * 0.05,
0.1 * 1.03 * 1.04 * 1.2 * 1.3,
1.01 * 1.02 * 0.1 * 1.03 * 1.04 * 1.2,
1.02 * 1.1 * 1.03 * 1.04 * 1.2 * 1.3,
1.01 * 1.02 * 1.03 * 1.04 * 0.1 * 1.2 * 1.3)
## -----------------------------------------------------------------
s <- 0.2
sboth <- (1/(1 + s)) - 1
m0 <- allFitnessEffects(data.frame(
parent = c("Root", "Root", "a1", "a2"),
child = c("a1", "a2", "b", "b"),
s = s,
sh = -1,
typeDep = "OR"),
epistasis = c("a1:a2" = sboth))
evalAllGenotypes(m0, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
s <- 0.2
m1 <- allFitnessEffects(data.frame(
parent = c("Root", "A"),
child = c("A", "B"),
s = s,
sh = -1,
typeDep = "OR"),
geneToModule = c("Root" = "Root",
"A" = "a1, a2",
"B" = "b1"))
evalAllGenotypes(m1, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
fnme <- allFitnessEffects(epistasis = c("A" = 0.1,
"B" = 0.2),
geneToModule = c("A" = "a1, a2",
"B" = "b1"))
evalAllGenotypes(fnme, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
fnme2 <- allFitnessEffects(epistasis = c("A" = 0.1,
"B" = 0.2),
geneToModule = c(
"Root" = "Root",
"A" = "a1, a2",
"B" = "b1"))
evalAllGenotypes(fnme, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
p4 <- data.frame(
parent = c(rep("Root", 4), "A", "B", "D", "E", "C", "F"),
child = c("A", "B", "D", "E", "C", "C", "F", "F", "G", "G"),
s = c(0.01, 0.02, 0.03, 0.04, 0.1, 0.1, 0.2, 0.2, 0.3, 0.3),
sh = c(rep(0, 4), c(-.9, -.9), c(-.95, -.95), c(-.99, -.99)),
typeDep = c(rep("--", 4),
"XMPN", "XMPN", "MN", "MN", "SM", "SM"))
fp4m <- allFitnessEffects(
p4,
geneToModule = c("Root" = "Root", "A" = "a1",
"B" = "b1, b2", "C" = "c1",
"D" = "d1, d2", "E" = "e1",
"F" = "f1, f2", "G" = "g1"))
## ---- fig.height=3------------------------------------------------
plot(fp4m)
## ---- fig.height=3------------------------------------------------
plot(fp4m, expandModules = TRUE)
## ---- fig.height=6------------------------------------------------
plot(fp4m, "igraph", layout = layout.reingold.tilford,
expandModules = TRUE)
## -----------------------------------------------------------------
gfp4 <- evalAllGenotypes(fp4m, order = FALSE, max = 1024)
## -----------------------------------------------------------------
gfp4[c(12, 20, 21, 40, 41, 46, 50, 55, 64, 92,
155, 157, 163, 372, 632, 828), ]
c(1.01 * 1.02, 1.02, 1.02 * 1.1, 0.1 * 1.3, 1.03,
1.03 * 1.04, 1.04 * 0.05, 0.05 * 1.3,
1.01 * 1.02 * 0.1, 1.02 * 1.1, 0.1 * 0.05 * 1.3,
1.03 * 0.05, 1.03 * 0.05, 1.03 * 1.04 * 1.2, 1.03 * 1.04 * 1.2,
1.02 * 1.1 * 1.03 * 1.04 * 1.2 * 1.3)
## -----------------------------------------------------------------
o3 <- allFitnessEffects(orderEffects = c(
"F > D > M" = -0.3,
"D > F > M" = 0.4,
"D > M > F" = 0.2,
"D > M" = 0.1,
"M > D" = 0.5),
geneToModule =
c("M" = "m",
"F" = "f",
"D" = "d") )
(ag <- evalAllGenotypes(o3, addwt = TRUE, order = TRUE))
## -----------------------------------------------------------------
ofe1 <- allFitnessEffects(
orderEffects = c("F > D" = -0.3, "D > F" = 0.4),
geneToModule =
c("F" = "f1, f2",
"D" = "d1, d2") )
ag <- evalAllGenotypes(ofe1, order = TRUE)
## -----------------------------------------------------------------
ag[5:16,]
## -----------------------------------------------------------------
ag[c(17, 39, 19, 29), ]
## -----------------------------------------------------------------
ag[c(17, 39, 19, 29), "Fitness"] == c(1.4, 0.7, 1.4, 0.7)
## -----------------------------------------------------------------
ag[c(43, 44),]
ag[c(43, 44), "Fitness"] == c(1.4, 1.4)
## -----------------------------------------------------------------
all(ag[41:52, "Fitness"] == 1.4)
## -----------------------------------------------------------------
all(ag[53:64, "Fitness"] == 0.7)
## -----------------------------------------------------------------
ofe2 <- allFitnessEffects(
orderEffects = c("F > D" = -0.3, "D > F" = 0.4),
geneToModule =
c("F" = "f1, f2, f3",
"D" = "d1, d2") )
ag2 <- evalAllGenotypes(ofe2, max = 325, order = TRUE)
## -----------------------------------------------------------------
all(ag2[grep("^d.*f.*", ag2[, 1]), "Fitness"] == 1.4)
all(ag2[grep("^f.*d.*", ag2[, 1]), "Fitness"] == 0.7)
oe <- c(grep("^f.*d.*", ag2[, 1]), grep("^d.*f.*", ag2[, 1]))
all(ag2[-oe, "Fitness"] == 1)
## -----------------------------------------------------------------
foi1 <- allFitnessEffects(
orderEffects = c("D>B" = -0.2, "B > D" = 0.3),
noIntGenes = c("A" = 0.05, "C" = -.2, "E" = .1))
## -----------------------------------------------------------------
foi1[c("geneModule", "long.geneNoInt")]
## -----------------------------------------------------------------
agoi1 <- evalAllGenotypes(foi1, max = 325, order = TRUE)
head(agoi1)
## -----------------------------------------------------------------
rn <- 1:nrow(agoi1)
names(rn) <- agoi1[, 1]
agoi1[rn[LETTERS[1:5]], "Fitness"] == c(1.05, 1, 0.8, 1, 1.1)
## -----------------------------------------------------------------
agoi1[grep("^A > [BD]$", names(rn)), "Fitness"] == 1.05
agoi1[grep("^C > [BD]$", names(rn)), "Fitness"] == 0.8
agoi1[grep("^E > [BD]$", names(rn)), "Fitness"] == 1.1
agoi1[grep("^[BD] > A$", names(rn)), "Fitness"] == 1.05
agoi1[grep("^[BD] > C$", names(rn)), "Fitness"] == 0.8
agoi1[grep("^[BD] > E$", names(rn)), "Fitness"] == 1.1
## -----------------------------------------------------------------
all.equal(agoi1[230:253, "Fitness"] ,
rep((1 - 0.2) * 1.05 * 0.8 * 1.1, 24))
## -----------------------------------------------------------------
sa <- 0.2
sb <- 0.3
sab <- 0.7
e2 <- allFitnessEffects(epistasis =
c("A: -B" = sa,
"-A:B" = sb,
"A : B" = sab))
evalAllGenotypes(e2, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
s2 <- ((1 + sab)/((1 + sa) * (1 + sb))) - 1
e3 <- allFitnessEffects(epistasis =
c("A" = sa,
"B" = sb,
"A : B" = s2))
evalAllGenotypes(e3, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
sa <- 0.1
sb <- 0.15
sc <- 0.2
sab <- 0.3
sbc <- -0.25
sabc <- 0.4
sac <- (1 + sa) * (1 + sc) - 1
E3A <- allFitnessEffects(epistasis =
c("A:-B:-C" = sa,
"-A:B:-C" = sb,
"-A:-B:C" = sc,
"A:B:-C" = sab,
"-A:B:C" = sbc,
"A:-B:C" = sac,
"A : B : C" = sabc)
)
evalAllGenotypes(E3A, order = FALSE, addwt = FALSE)
## -----------------------------------------------------------------
sa <- 0.1
sb <- 0.15
sc <- 0.2
sab <- 0.3
Sab <- ( (1 + sab)/((1 + sa) * (1 + sb))) - 1
Sbc <- ( (1 + sbc)/((1 + sb) * (1 + sc))) - 1
Sabc <- ( (1 + sabc)/
( (1 + sa) * (1 + sb) * (1 + sc) *
(1 + Sab) * (1 + Sbc) ) ) - 1
E3B <- allFitnessEffects(epistasis =
c("A" = sa,
"B" = sb,
"C" = sc,
"A:B" = Sab,
"B:C" = Sbc,
## "A:C" = sac, ## not needed now
"A : B : C" = Sabc)
)
evalAllGenotypes(E3B, order = FALSE, addwt = FALSE)
## -----------------------------------------------------------------
all(evalAllGenotypes(E3A, order = FALSE, addwt = FALSE) ==
evalAllGenotypes(E3B, order = FALSE, addwt = FALSE))
## -----------------------------------------------------------------
sa <- 0.2
sb <- 0.3
sab <- 0.7
em <- allFitnessEffects(epistasis =
c("A: -B" = sa,
"-A:B" = sb,
"A : B" = sab),
geneToModule = c("A" = "a1, a2",
"B" = "b1, b2"))
evalAllGenotypes(em, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
s2 <- ((1 + sab)/((1 + sa) * (1 + sb))) - 1
em2 <- allFitnessEffects(epistasis =
c("A" = sa,
"B" = sb,
"A : B" = s2),
geneToModule = c("A" = "a1, a2",
"B" = "b1, b2")
)
evalAllGenotypes(em2, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
fnme <- allFitnessEffects(epistasis = c("A" = 0.1,
"B" = 0.2),
geneToModule = c("A" = "a1, a2",
"B" = "b1, b2, b3"))
evalAllGenotypes(fnme, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
fnme <- allFitnessEffects(epistasis = c("A" = 0.1,
"B" = 0.2,
"A : B" = 0.0),
geneToModule = c("A" = "a1, a2",
"B" = "b1, b2, b3"))
evalAllGenotypes(fnme, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
s <- 0.2
sv <- allFitnessEffects(epistasis = c("-A : B" = -1,
"A : -B" = -1,
"A:B" = s))
## -----------------------------------------------------------------
(asv <- evalAllGenotypes(sv, order = FALSE, addwt = TRUE))
## -----------------------------------------------------------------
evalAllGenotypes(sv, order = TRUE, addwt = TRUE)
## -----------------------------------------------------------------
sa <- -0.1
sb <- -0.2
sab <- 0.25
sv2 <- allFitnessEffects(epistasis = c("-A : B" = sb,
"A : -B" = sa,
"A:B" = sab),
geneToModule = c(
"A" = "a1, a2",
"B" = "b"))
evalAllGenotypes(sv2, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
evalAllGenotypes(sv2, order = TRUE, addwt = TRUE)
## -----------------------------------------------------------------
sa <- 0.1
sb <- 0.2
sab <- -0.8
sm1 <- allFitnessEffects(epistasis = c("-A : B" = sb,
"A : -B" = sa,
"A:B" = sab))
evalAllGenotypes(sm1, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
evalAllGenotypes(sm1, order = TRUE, addwt = TRUE)
## -----------------------------------------------------------------
evalAllGenotypes(sv, order = FALSE, addwt = TRUE, model = "Bozic")
## -----------------------------------------------------------------
s <- 0.2
svB <- allFitnessEffects(epistasis = c("-A : B" = -Inf,
"A : -B" = -Inf,
"A:B" = s))
evalAllGenotypes(svB, order = FALSE, addwt = TRUE, model = "Bozic")
## -----------------------------------------------------------------
s <- 1
svB1 <- allFitnessEffects(epistasis = c("-A : B" = -Inf,
"A : -B" = -Inf,
"A:B" = s))
evalAllGenotypes(svB1, order = FALSE, addwt = TRUE, model = "Bozic")
s <- 3
svB3 <- allFitnessEffects(epistasis = c("-A : B" = -Inf,
"A : -B" = -Inf,
"A:B" = s))
evalAllGenotypes(svB3, order = FALSE, addwt = TRUE, model = "Bozic")
## -----------------------------------------------------------------
i1 <- allFitnessEffects(noIntGenes = c(1, 0.5))
evalAllGenotypes(i1, order = FALSE, addwt = TRUE,
model = "Bozic")
i1_b <- oncoSimulIndiv(i1, model = "Bozic")
## -----------------------------------------------------------------
evalAllGenotypes(i1, order = FALSE, addwt = TRUE,
model = "Exp")
i1_e <- oncoSimulIndiv(i1, model = "Exp")
summary(i1_e)
## -----------------------------------------------------------------
p4 <- data.frame(
parent = c(rep("Root", 4), "A", "B", "D", "E", "C", "F"),
child = c("A", "B", "D", "E", "C", "C", "F", "F", "G", "G"),
s = c(0.01, 0.02, 0.03, 0.04, 0.1, 0.1, 0.2, 0.2, 0.3, 0.3),
sh = c(rep(0, 4), c(-.9, -.9), c(-.95, -.95), c(-.99, -.99)),
typeDep = c(rep("--", 4),
"XMPN", "XMPN", "MN", "MN", "SM", "SM"))
oe <- c("C > F" = -0.1, "H > I" = 0.12)
sm <- c("I:J" = -1)
sv <- c("-K:M" = -.5, "K:-M" = -.5)
epist <- c(sm, sv)
modules <- c("Root" = "Root", "A" = "a1",
"B" = "b1, b2", "C" = "c1",
"D" = "d1, d2", "E" = "e1",
"F" = "f1, f2", "G" = "g1",
"H" = "h1, h2", "I" = "i1",
"J" = "j1, j2", "K" = "k1, k2", "M" = "m1")
set.seed(1) ## for reproducibility
noint <- rexp(5, 10)
names(noint) <- paste0("n", 1:5)
fea <- allFitnessEffects(rT = p4, epistasis = epist,
orderEffects = oe,
noIntGenes = noint,
geneToModule = modules)
## ---- fig.height=5.5----------------------------------------------
plot(fea)
## ---- fig.height=5.5----------------------------------------------
plot(fea, "igraph")
## ---- fig.height=5.5----------------------------------------------
plot(fea, expandModules = TRUE)
## ---- fig.height=6.5----------------------------------------------
plot(fea, "igraph", expandModules = TRUE)
## -----------------------------------------------------------------
evalGenotype("k1 > i1 > h2", fea) ## 0.5
evalGenotype("k1 > h1 > i1", fea) ## 0.5 * 1.12
evalGenotype("k2 > m1 > h1 > i1", fea) ## 1.12
evalGenotype("k2 > m1 > h1 > i1 > c1 > n3 > f2", fea)
## 1.12 * 0.1 * (1 + noint[3]) * 0.05 * 0.9
## -----------------------------------------------------------------
randomGenotype <- function(fe, ns = NULL) {
gn <- setdiff(c(fe$geneModule$Gene,
fe$long.geneNoInt$Gene), "Root")
if(is.null(ns)) ns <- sample(length(gn), 1)
return(paste(sample(gn, ns), collapse = " > "))
}
set.seed(2) ## for reproducibility
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: k2 > i1 > c1 > n1 > m1
## Individual s terms are : 0.0755182 -0.9
## Fitness: 0.107552
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: n2 > h1 > h2
## Individual s terms are : 0.118164
## Fitness: 1.11816
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: d2 > k2 > c1 > f2 > n4 > m1 > n3 > f1 > b1 > g1 > n5 > h1 > j2
## Individual s terms are : 0.0145707 0.0139795 0.0436069 0.02 0.1 0.03 -0.95 0.3 -0.1
## Fitness: 0.0725829
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: h2 > c1 > f1 > n2 > b2 > a1 > n1 > i1
## Individual s terms are : 0.0755182 0.118164 0.01 0.02 -0.9 -0.95 -0.1 0.12
## Fitness: 0.00624418
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: h2 > j1 > m1 > d2 > i1 > b2 > k2 > d1 > b1 > n3 > n1 > g1 > h1 > c1 > k1 > e1 > a1 > f1 > n5 > f2
## Individual s terms are : 0.0755182 0.0145707 0.0436069 0.01 0.02 -0.9 0.03 0.04 0.2 0.3 -1 -0.1 0.12
## Fitness: 0
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: n1 > m1 > n3 > i1 > j1 > n5 > k1
## Individual s terms are : 0.0755182 0.0145707 0.0436069 -1
## Fitness: 0
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: d2 > n1 > g1 > f1 > f2 > c1 > b1 > d1 > k1 > a1 > b2 > i1 > n4 > h2 > n2
## Individual s terms are : 0.0755182 0.118164 0.0139795 0.01 0.02 -0.9 0.03 -0.95 0.3 -0.5
## Fitness: 0.00420528
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: j1 > f1 > j2 > a1 > n4 > c1 > n3 > k1 > d1 > h1
## Individual s terms are : 0.0145707 0.0139795 0.01 0.1 0.03 -0.95 -0.5
## Fitness: 0.0294308
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: n5 > f2 > f1 > h2 > n4 > c1 > n3 > b1
## Individual s terms are : 0.0145707 0.0139795 0.0436069 0.02 0.1 -0.95
## Fitness: 0.0602298
evalGenotype(randomGenotype(fea), fea, echo = TRUE, verbose = TRUE)
## Genotype: h1 > d1 > f2
## Individual s terms are : 0.03 -0.95
## Fitness: 0.0515
## -----------------------------------------------------------------
muvar2 <- c("U" = 1e-6, "z" = 5e-5, "e" = 5e-4, "m" = 5e-3,
"D" = 1e-4)
ni1 <- rep(0, 5)
names(ni1) <- names(muvar2) ## We use the same names, of course
fe1 <- allFitnessEffects(noIntGenes = ni1)
bb <- oncoSimulIndiv(fe1,
mu = muvar2, onlyCancer = FALSE,
initSize = 1e5,
finalTime = 25,
seed =NULL)
## -----------------------------------------------------------------
fe2 <- allFitnessEffects(noIntGenes =
c(a1 = 0.1, a2 = 0.2,
b1 = 0.01, b2 = 0.3, b3 = 0.2,
c1 = 0.3, c2 = -0.2))
fm2 <- allMutatorEffects(epistasis = c("A" = 5,
"B" = 10,
"C" = 3),
geneToModule = c("A" = "a1, a2",
"B" = "b1, b2, b3",
"C" = "c1, c2"))
## Show the fitness effect of a specific genotype
evalGenotype("a1, c2", fe2, verbose = TRUE)
## Show the mutator effect of a specific genotype
evalGenotypeMut("a1, c2", fm2, verbose = TRUE)
## Fitness and mutator of a specific genotype
evalGenotypeFitAndMut("a1, c2", fe2, fm2, verbose = TRUE)
## ---- eval=FALSE--------------------------------------------------
# ## Show only all the fitness effects
# evalAllGenotypes(fe2, order = FALSE)
#
# ## Show only all mutator effects
# evalAllGenotypesMut(fm2)
#
# ## Show all fitness and mutator
# evalAllGenotypesFitAndMut(fe2, fm2, order = FALSE)
## -----------------------------------------------------------------
set.seed(1) ## for reproducibility
## 17 genes, 7 with no direct fitness effects
ni <- c(rep(0, 7), runif(10, min = -0.01, max = 0.1))
names(ni) <- c("a1", "a2", "b1", "b2", "b3", "c1", "c2",
paste0("g", 1:10))
fe3 <- allFitnessEffects(noIntGenes = ni)
fm3 <- allMutatorEffects(epistasis = c("A" = 5,
"B" = 10,
"C" = 3,
"A:C" = 70),
geneToModule = c("A" = "a1, a2",
"B" = "b1, b2, b3",
"C" = "c1, c2"))
## -----------------------------------------------------------------
## These only affect mutation, not fitness
evalGenotypeFitAndMut("a1, a2", fe3, fm3, verbose = TRUE)
evalGenotypeFitAndMut("a1, b3", fe3, fm3, verbose = TRUE)
## These only affect fitness: the mutator multiplier is 1
evalGenotypeFitAndMut("g1", fe3, fm3, verbose = TRUE)
evalGenotypeFitAndMut("g3, g9", fe3, fm3, verbose = TRUE)
## These affect both
evalGenotypeFitAndMut("g3, g9, a2, b3", fe3, fm3, verbose = TRUE)
## -----------------------------------------------------------------
set.seed(1) ## so that it is easy to reproduce
mue1 <- oncoSimulIndiv(fe3, muEF = fm3,
mu = 1e-6,
initSize = 1e5,
model = "McFL",
detectionSize = 5e6,
finalTime = 500,
onlyCancer = FALSE)
## ---- eval=FALSE--------------------------------------------------
# ## We do not show this in the vignette to avoid cluttering it
# ## with output
# mue1
## ---- eval=FALSE--------------------------------------------------
#
# set.seed(1) ## for reproducibility
# ## 17 genes, 7 with no direct fitness effects
# ni <- c(rep(0, 7), runif(10, min = -0.01, max = 0.1))
# names(ni) <- c("a1", "a2", "b1", "b2", "b3", "c1", "c2",
# paste0("g", 1:10))
#
# ## Next is for nicer figure labeling.
# ## Consider as drivers genes with s >0
# gp <- which(ni > 0)
#
# fe3 <- allFitnessEffects(noIntGenes = ni,
# drvNames = names(ni)[gp])
#
#
# set.seed(12)
# mue1 <- oncoSimulIndiv(fe3, muEF = fm3,
# mu = 1e-6,
# initSize = 1e5,
# model = "McFL",
# detectionSize = 5e6,
# finalTime = 270,
# keepPhylog = TRUE,
# onlyCancer = FALSE)
# mue1
# ## If you decrease N even further it gets even more cluttered
# op <- par(ask = TRUE)
# plotClonePhylog(mue1, N = 10, timeEvents = TRUE)
# plot(mue1, plotDrivers = TRUE, addtot = TRUE,
# plotDiversity = TRUE)
#
# ## The stacked plot is slow; be patient
# ## Most clones have tiny population sizes, and their lines
# ## are piled on top of each other
# plot(mue1, addtot = TRUE,
# plotDiversity = TRUE, type = "stacked")
# par(op)
## -----------------------------------------------------------------
d1 <- -0.05 ## single mutant fitness 0.95
d2 <- -0.08 ## double mutant fitness 0.92
d3 <- 0.2 ## triple mutant fitness 1.2
s2 <- ((1 + d2)/(1 + d1)^2) - 1
s3 <- ( (1 + d3)/((1 + d1)^3 * (1 + s2)^3) ) - 1
wb <- allFitnessEffects(
epistasis = c(
"A" = d1,
"B" = d1,
"C" = d1,
"A:B" = s2,
"A:C" = s2,
"B:C" = s2,
"A:B:C" = s3))
## ---- fig.width=6.5, fig.height=5---------------------------------
plotFitnessLandscape(wb, use_ggrepel = TRUE)
## ---- fig.width=6.5, fig.height=5---------------------------------
(ewb <- evalAllGenotypes(wb, order = FALSE))
plot(ewb, use_ggrepel = TRUE)
## ----wasthis111, fig.width=9.5, fig.height=9.5--------------------
par(cex = 0.7)
pancr <- allFitnessEffects(
data.frame(parent = c("Root", rep("KRAS", 4),
"SMAD4", "CDNK2A",
"TP53", "TP53", "MLL3"),
child = c("KRAS","SMAD4", "CDNK2A",
"TP53", "MLL3",
rep("PXDN", 3), rep("TGFBR2", 2)),
s = 0.1,
sh = -0.9,
typeDep = "MN"))
plot(evalAllGenotypes(pancr, order = FALSE), use_ggrepel = TRUE)
## -----------------------------------------------------------------
K <- 4
sp <- 1e-5
sdp <- 0.015
sdplus <- 0.05
sdminus <- 0.1
cnt <- (1 + sdplus)/(1 + sdminus)
prod_cnt <- cnt - 1
bauer <- data.frame(parent = c("Root", rep("D", K)),
child = c("D", paste0("s", 1:K)),
s = c(prod_cnt, rep(sdp, K)),
sh = c(0, rep(sp, K)),
typeDep = "MN")
fbauer <- allFitnessEffects(bauer)
(b1 <- evalAllGenotypes(fbauer, order = FALSE, addwt = TRUE))
## ---- fig.height=3------------------------------------------------
plot(fbauer)
## ---- fig.width=6, fig.height=6-----------------------------------
plot(b1, use_ggrepel = TRUE)
## -----------------------------------------------------------------
m1 <- expand.grid(D = c(1, 0), s1 = c(1, 0), s2 = c(1, 0),
s3 = c(1, 0), s4 = c(1, 0))
fitness_bauer <- function(D, s1, s2, s3, s4,
sp = 1e-5, sdp = 0.015, sdplus = 0.05,
sdminus = 0.1) {
if(!D) {
b <- 0.5 * ( (1 + sp)^(sum(c(s1, s2, s3, s4))))
} else {
b <- 0.5 *
(((1 + sdplus)/(1 + sdminus) *
(1 + sdp)^(sum(c(s1, s2, s3, s4)))))
}
fitness <- b - (1 - b)
our_fitness <- 1 + fitness ## prevent negative fitness and
## make wt fitness = 1
return(our_fitness)
}
m1$Fitness <-
apply(m1, 1, function(x) do.call(fitness_bauer, as.list(x)))
bauer2 <- allFitnessEffects(genotFitness = m1)
## -----------------------------------------------------------------
evalAllGenotypes(bauer2, order = FALSE, addwt = TRUE)
## ---- echo=FALSE, fig.height=4, fig.width=4-----------------------
df1 <- data.frame(x = c(1, 1.2, 1.4), f = c(1, 1.2, 1.2),
names = c("wt", "A", "B"))
plot(df1[, 2] ~ df1[, 1], axes = TRUE, xlab= "",
ylab = "Fitness", xaxt = "n", yaxt = "n", ylim = c(1, 1.21))
segments(1, 1, 1.2, 1.2)
segments(1, 1, 1.4, 1.2)
text(1, 1, "wt", pos = 4)
text(1.2, 1.2, "A", pos = 2)
text(1.4, 1.2, "B", pos = 2)
## axis(1, tick = FALSE, labels = FALSE)
## axis(2, tick = FALSE, labels = FALSE)
## -----------------------------------------------------------------
s <- 0.1 ## or whatever number
m1a1 <- allFitnessEffects(data.frame(parent = c("Root", "Root"),
child = c("A", "B"),
s = s,
sh = 0,
typeDep = "MN"))
evalAllGenotypes(m1a1, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
s <- 0.1
sab <- 0.3
m1a2 <- allFitnessEffects(epistasis = c("A:-B" = s,
"-A:B" = s,
"A:B" = sab))
evalAllGenotypes(m1a2, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
sab3 <- ((1 + sab)/((1 + s)^2)) - 1
m1a3 <- allFitnessEffects(data.frame(parent = c("Root", "Root"),
child = c("A", "B"),
s = s,
sh = 0,
typeDep = "MN"),
epistasis = c("A:B" = sab3))
evalAllGenotypes(m1a3, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
all.equal(evalAllGenotypes(m1a2, order = FALSE, addwt = TRUE),
evalAllGenotypes(m1a3, order = FALSE, addwt = TRUE))
## ---- echo=FALSE, fig.width=4, fig.height=4-----------------------
df1 <- data.frame(x = c(1, 1.2, 1.2, 1.4), f = c(1, 0.4, 0.3, 1.3),
names = c("wt", "A", "B", "AB"))
plot(df1[, 2] ~ df1[, 1], axes = TRUE, xlab= "", ylab = "Fitness",
xaxt = "n", yaxt = "n", ylim = c(0.29, 1.32))
segments(1, 1, 1.2, 0.4)
segments(1, 1, 1.2, 0.3)
segments(1.2, 0.4, 1.4, 1.3)
segments(1.2, 0.3, 1.4, 1.3)
text(x = df1[, 1], y = df1[, 2], labels = df1[, "names"], pos = c(4, 2, 2, 2))
## text(1, 1, "wt", pos = 4)
## text(1.2, 1.2, "A", pos = 2)
## text(1.4, 1.2, "B", pos = 2)
## -----------------------------------------------------------------
sa <- -0.6
sb <- -0.7
sab <- 0.3
m1b1 <- allFitnessEffects(epistasis = c("A:-B" = sa,
"-A:B" = sb,
"A:B" = sab))
evalAllGenotypes(m1b1, order = FALSE, addwt = TRUE)
## ---- echo=FALSE, fig.width=4, fig.height=4-----------------------
df1 <- data.frame(x = c(1, 1.2, 1.2, 1.4), f = c(1, 1.2, 0.7, 1.5),
names = c("wt", "A", "B", "AB"))
plot(df1[, 2] ~ df1[, 1], axes = TRUE, xlab = "", ylab = "Fitness",
xaxt = "n", yaxt = "n", ylim = c(0.69, 1.53))
segments(1, 1, 1.2, 1.2)
segments(1, 1, 1.2, 0.7)
segments(1.2, 1.2, 1.4, 1.5)
segments(1.2, 0.7, 1.4, 1.5)
text(x = df1[, 1], y = df1[, 2], labels = df1[, "names"], pos = c(3, 3, 3, 2))
## text(1, 1, "wt", pos = 4)
## text(1.2, 1.2, "A", pos = 2)
## text(1.4, 1.2, "B", pos = 2)
## -----------------------------------------------------------------
sa <- 0.2
sb <- -0.3
sab <- 0.5
m1c1 <- allFitnessEffects(epistasis = c("A:-B" = sa,
"-A:B" = sb,
"A:B" = sab))
evalAllGenotypes(m1c1, order = FALSE, addwt = TRUE)
## ---- echo=FALSE, fig.width=4.5, fig.height=3.5-------------------
df1 <- data.frame(x = c(1, 2, 3, 4), f = c(1.1, 1, 0.95, 1.2),
names = c("u", "wt", "i", "v"))
plot(df1[, 2] ~ df1[, 1], axes = FALSE, xlab = "", ylab = "")
par(las = 1)
axis(2)
axis(1, at = c(1, 2, 3, 4), labels = df1[, "names"], ylab = "")
box()
arrows(c(2, 2, 3), c(1, 1, 0.95),
c(1, 3, 4), c(1.1, 0.95, 1.2))
## text(1, 1, "wt", pos = 4)
## text(1.2, 1.2, "A", pos = 2)
## text(1.4, 1.2, "B", pos = 2)
## -----------------------------------------------------------------
su <- 0.1
si <- -0.05
fvi <- 1.2 ## the fitness of the vi mutant
sv <- (fvi/(1 + si)) - 1
sui <- suv <- -1
od <- allFitnessEffects(
data.frame(parent = c("Root", "Root", "i"),
child = c("u", "i", "v"),
s = c(su, si, sv),
sh = -1,
typeDep = "MN"),
epistasis = c(
"u:i" = sui,
"u:v" = suv))
## ---- fig.width=3, fig.height=3-----------------------------------
plot(od)
## -----------------------------------------------------------------
evalAllGenotypes(od, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
u <- 0.1; i <- -0.05; vi <- (1.2/0.95) - 1; ui <- uv <- -Inf
od2 <- allFitnessEffects(
epistasis = c("u" = u, "u:i" = ui,
"u:v" = uv, "i" = i,
"v:-i" = -Inf, "v:i" = vi))
evalAllGenotypes(od2, addwt = TRUE)
## ---- echo=FALSE, fig.width=4, fig.height=3-----------------------
df1 <- data.frame(x = c(1, 2, 3), f = c(1, 0.95, 1.2),
names = c("wt", "1", "2"))
plot(df1[, 2] ~ df1[, 1], axes = FALSE, xlab = "", ylab = "")
par(las = 1)
axis(2)
axis(1, at = c(1, 2, 3), labels = df1[, "names"], ylab = "")
box()
segments(c(1, 2), c(1, 0.95),
c(2, 3), c(0.95, 1.2))
## text(1, 1, "wt", pos = 4)
## text(1.2, 1.2, "A", pos = 2)
## text(1.4, 1.2, "B", pos = 2)
## ---- echo=FALSE, fig.width=4, fig.height=3-----------------------
df1 <- data.frame(x = c(1, 2, 3, 4), f = c(1, 0.95, 0.92, 1.2),
names = c("wt", "1", "2", "3"))
plot(df1[, 2] ~ df1[, 1], axes = FALSE, xlab = "", ylab = "")
par(las = 1)
axis(2)
axis(1, at = c(1, 2, 3, 4), labels = df1[, "names"], ylab = "")
box()
segments(c(1, 2, 3), c(1, 0.95, 0.92),
c(2, 3, 4), c(0.95, 0.92, 1.2))
## text(1, 1, "wt", pos = 4)
## text(1.2, 1.2, "A", pos = 2)
## text(1.4, 1.2, "B", pos = 2)
## -----------------------------------------------------------------
d1 <- -0.05 ## single mutant fitness 0.95
d2 <- -0.08 ## double mutant fitness 0.92
d3 <- 0.2 ## triple mutant fitness 1.2
s2 <- ((1 + d2)/(1 + d1)^2) - 1
s3 <- ( (1 + d3)/((1 + d1)^3 * (1 + s2)^3) ) - 1
w <- allFitnessEffects(
data.frame(parent = c("Root", "Root", "Root"),
child = c("A", "B", "C"),
s = d1,
sh = -1,
typeDep = "MN"),
epistasis = c(
"A:B" = s2,
"A:C" = s2,
"B:C" = s2,
"A:B:C" = s3))
## ---- fig.width=4, fig.height=4-----------------------------------
plot(w)
## -----------------------------------------------------------------
evalAllGenotypes(w, order = FALSE, addwt = TRUE)
## -----------------------------------------------------------------
wb <- allFitnessEffects(
epistasis = c(
"A" = d1,
"B" = d1,
"C" = d1,
"A:B" = s2,
"A:C" = s2,
"B:C" = s2,
"A:B:C" = s3))
evalAllGenotypes(wb, order = FALSE, addwt = TRUE)
## ---- , fig.width=3, fig.height=3---------------------------------
plot(wb)
## -----------------------------------------------------------------
wc <- allFitnessEffects(
epistasis = c(
"A:-B:-C" = d1,
"B:-C:-A" = d1,
"C:-A:-B" = d1,
"A:B:-C" = d2,
"A:C:-B" = d2,
"B:C:-A" = d2,
"A:B:C" = d3))
evalAllGenotypes(wc, order = FALSE, addwt = TRUE)
## ---- fig.width=4-------------------------------------------------
pancr <- allFitnessEffects(
data.frame(parent = c("Root", rep("KRAS", 4),
"SMAD4", "CDNK2A",
"TP53", "TP53", "MLL3"),
child = c("KRAS","SMAD4", "CDNK2A",
"TP53", "MLL3",
rep("PXDN", 3), rep("TGFBR2", 2)),
s = 0.1,
sh = -0.9,
typeDep = "MN"))
plot(pancr)
## ---- fig.height = 4----------------------------------------------
rv1 <- allFitnessEffects(data.frame(parent = c("Root", "A", "KRAS"),
child = c("A", "KRAS", "FBXW7"),
s = 0.1,
sh = -0.01,
typeDep = "MN"),
geneToModule = c("Root" = "Root",
"A" = "EVC2, PIK3CA, TP53",
"KRAS" = "KRAS",
"FBXW7" = "FBXW7"))
plot(rv1, expandModules = TRUE, autofit = TRUE)
## ---- fig.height=6------------------------------------------------
rv2 <- allFitnessEffects(
data.frame(parent = c("Root", "1", "2", "3", "4"),
child = c("1", "2", "3", "4", "ELF3"),
s = 0.1,
sh = -0.01,
typeDep = "MN"),
geneToModule = c("Root" = "Root",
"1" = "APC, FBXW7",
"2" = "ATM, FAM123B, PIK3CA, TP53",
"3" = "BRAF, KRAS, NRAS",
"4" = "SMAD2, SMAD4, SOX9",
"ELF3" = "ELF3"))
plot(rv2, expandModules = TRUE, autofit = TRUE)
## ----seedprbau003, echo=FALSE-------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## ----prbau003, fig.height=6---------------------------------------
o3init <- allFitnessEffects(orderEffects = c(
"M > D > F" = 0.99,
"D > M > F" = 0.2,
"D > M" = 0.1,
"M > D" = 0.9),
noIntGenes = c("u" = 0.01,
"v" = 0.01,
"w" = 0.001,
"x" = 0.0001,
"y" = -0.0001,
"z" = -0.001),
geneToModule =
c("M" = "m",
"F" = "f",
"D" = "d") )
oneI <- oncoSimulIndiv(o3init, model = "McFL",
mu = 5e-5, finalTime = 200,
detectionDrivers = 3,
onlyCancer = FALSE,
initSize = 1000,
keepPhylog = TRUE,
initMutant = c("m > u > d")
)
plotClonePhylog(oneI, N = 0)
## ----prbau003bb, fig.height=6-------------------------------------
## Note we also disable the stopping stochastically as a function of size
## to allow the population to grow large and generate may different
## clones.
## For speed, we set a small finalTime and we fix the seed
## for reproducilibity. Beware: since finalTime is short, sometimes
## we do not reach cancer
set.seed(1)
RNGkind("L'Ecuyer-CMRG")
ospI <- oncoSimulPop(2,
o3init, model = "Exp",
mu = 5e-5, finalTime = 200,
detectionDrivers = 3,
onlyCancer = TRUE,
initSize = 10,
keepPhylog = TRUE,
initMutant = c("d > m > z"),
mc.cores = 2,
seed = NULL
)
## Show just one example
## op <- par(mar = rep(0, 4), mfrow = c(1, 2))
plotClonePhylog(ospI[[1]])
## plotClonePhylog(ospI[[2]])
## par(op)
set.seed(1)
RNGkind("L'Ecuyer-CMRG")
ossI <- oncoSimulSample(2,
o3init, model = "Exp",
mu = 5e-5, finalTime = 200,
detectionDrivers = 2,
onlyCancer = TRUE,
initSize = 10,
initMutant = c("z > d"),
## check presence of initMutant:
thresholdWhole = 1,
seed = NULL
)
## No phylogeny is kept with oncoSimulSample, but look at the
## OcurringDrivers and the sample
ossI$popSample
ossI$popSummary[, "OccurringDrivers", drop = FALSE]
## ----prbaux002, eval=FALSE----------------------------------------
# gi2 <- rep(0, 5)
# names(gi2) <- letters[1:5]
# oi2 <- allFitnessEffects(noIntGenes = gi2)
# s5 <- oncoSimulPop(200,
# oi2,
# model = "McFL",
# initSize = 1000,
# detectionProb = c(p2 = 0.1,
# n2 = 2000,
# PDBaseline = 1000,
# checkSizePEvery = 2),
# detectionSize = NA,
# finalTime = NA,
# keepEvery = NA,
# detectionDrivers = NA)
# s5
# hist(unlist(lapply(s5, function(x) x$FinalTime)))
## -----------------------------------------------------------------
u <- 0.2; i <- -0.02; vi <- 0.6; ui <- uv <- -Inf
od2 <- allFitnessEffects(
epistasis = c("u" = u, "u:i" = ui,
"u:v" = uv, "i" = i,
"v:-i" = -Inf, "v:i" = vi))
## ----simul-ochs---------------------------------------------------
initS <- 20
## We use only a small number of repetitions for the sake
## of speed. Even fewer in Windows, since we run on a single
## core
if(.Platform$OS.type == "windows") {
nruns <- 4
} else {
nruns <- 10
}
od100 <- oncoSimulPop(nruns, od2,
fixation = c("u", "v, i"),
model = "McFL",
mu = 1e-4,
detectionDrivers = NA,
finalTime = NA,
detectionSize = NA,
detectionProb = NA,
onlyCancer = TRUE,
initSize = initS,
mc.cores = 2)
## ----ochs-freq-genots---------------------------------------------
sampledGenotypes(samplePop(od100))
## ----sum-simul-ochs-----------------------------------------------
head(summary(od100)[, c(1:3, 8:9)])
## ----fixationG1---------------------------------------------------
## Create a simple fitness landscape
rl1 <- matrix(0, ncol = 6, nrow = 9)
colnames(rl1) <- c(LETTERS[1:5], "Fitness")
rl1[1, 6] <- 1
rl1[cbind((2:4), c(1:3))] <- 1
rl1[2, 6] <- 1.4
rl1[3, 6] <- 1.32
rl1[4, 6] <- 1.32
rl1[5, ] <- c(0, 1, 0, 0, 1, 1.5)
rl1[6, ] <- c(0, 0, 1, 1, 0, 1.54)
rl1[7, ] <- c(1, 0, 1, 1, 0, 1.65)
rl1[8, ] <- c(1, 1, 1, 1, 0, 1.75)
rl1[9, ] <- c(1, 1, 1, 1, 1, 1.85)
class(rl1) <- c("matrix", "genotype_fitness_matrix")
## plot(rl1) ## to see the fitness landscape
## Gene combinations
local_max_g <- c("A", "B, E", "A, B, C, D, E")
## Specify the genotypes
local_max <- paste0("_,", local_max_g)
fr1 <- allFitnessEffects(genotFitness = rl1, drvNames = LETTERS[1:5])
initS <- 2000
######## Stop on gene combinations #####
r1 <- oncoSimulPop(10,
fp = fr1,
model = "McFL",
initSize = initS,
mu = 1e-4,
detectionSize = NA,
sampleEvery = .03,
keepEvery = 1,
finalTime = 50000,
fixation = local_max_g,
detectionDrivers = NA,
detectionProb = NA,
onlyCancer = TRUE,
max.num.tries = 500,
max.wall.time = 20,
errorHitMaxTries = TRUE,
keepPhylog = FALSE,
mc.cores = 2)
sp1 <- samplePop(r1, "last", "singleCell")
sgsp1 <- sampledGenotypes(sp1)
## often you will stop on gene combinations that
## are not local maxima in the fitness landscape
sgsp1
sgsp1$Genotype %in% local_max_g
####### Stop on genotypes ####
r2 <- oncoSimulPop(10,
fp = fr1,
model = "McFL",
initSize = initS,
mu = 1e-4,
detectionSize = NA,
sampleEvery = .03,
keepEvery = 1,
finalTime = 50000,
fixation = local_max,
detectionDrivers = NA,
detectionProb = NA,
onlyCancer = TRUE,
max.num.tries = 500,
max.wall.time = 20,
errorHitMaxTries = TRUE,
keepPhylog = FALSE,
mc.cores = 2)
## All final genotypes should be local maxima
sp2 <- samplePop(r2, "last", "singleCell")
sgsp2 <- sampledGenotypes(sp2)
sgsp2$Genotype %in% local_max_g
## ----fixationG2---------------------------------------------------
## Create a simple fitness landscape
rl1 <- matrix(0, ncol = 6, nrow = 9)
colnames(rl1) <- c(LETTERS[1:5], "Fitness")
rl1[1, 6] <- 1
rl1[cbind((2:4), c(1:3))] <- 1
rl1[2, 6] <- 1.4
rl1[3, 6] <- 1.32
rl1[4, 6] <- 1.32
rl1[5, ] <- c(0, 1, 0, 0, 1, 1.5)
rl1[6, ] <- c(0, 0, 1, 1, 0, 1.54)
rl1[7, ] <- c(1, 0, 1, 1, 0, 1.65)
rl1[8, ] <- c(1, 1, 1, 1, 0, 1.75)
rl1[9, ] <- c(1, 1, 1, 1, 1, 1.85)
class(rl1) <- c("matrix", "genotype_fitness_matrix")
## plot(rl1) ## to see the fitness landscape
## The local fitness maxima are
## c("A", "B, E", "A, B, C, D, E")
fr1 <- allFitnessEffects(genotFitness = rl1, drvNames = LETTERS[1:5])
initS <- 2000
## Stop on genotypes
r3 <- oncoSimulPop(10,
fp = fr1,
model = "McFL",
initSize = initS,
mu = 1e-4,
detectionSize = NA,
sampleEvery = .03,
keepEvery = 1,
finalTime = 50000,
fixation = c(paste0("_,",
c("A", "B, E", "A, B, C, D, E")),
fixation_tolerance = 0.1,
min_successive_fixation = 200,
fixation_min_size = 3000),
detectionDrivers = NA,
detectionProb = NA,
onlyCancer = TRUE,
max.num.tries = 500,
max.wall.time = 20,
errorHitMaxTries = TRUE,
keepPhylog = FALSE,
mc.cores = 2)
## ----prbaux001----------------------------------------------------
K <- 5
sd <- 0.1
sdp <- 0.15
sp <- 0.05
bauer <- data.frame(parent = c("Root", rep("p", K)),
child = c("p", paste0("s", 1:K)),
s = c(sd, rep(sdp, K)),
sh = c(0, rep(sp, K)),
typeDep = "MN")
fbauer <- allFitnessEffects(bauer, drvNames = "p")
set.seed(1)
## Use fairly large mutation rate
b1 <- oncoSimulIndiv(fbauer, mu = 5e-5, initSize = 1000,
finalTime = NA,
onlyCancer = TRUE,
detectionProb = "default")
## ----baux1,fig.width=6.5, fig.height=10, fig.cap="Three drivers' plots of a simulation of Bauer's model"----
par(mfrow = c(3, 1))
## First, drivers
plot(b1, type = "line", addtot = TRUE)
plot(b1, type = "stacked")
plot(b1, type = "stream")
## ----baux2,fig.width=6.5, fig.height=10, fig.cap="Three genotypes' plots of a simulation of Bauer's model"----
par(mfrow = c(3, 1))
## Next, genotypes
plot(b1, show = "genotypes", type = "line")
plot(b1, show = "genotypes", type = "stacked")
plot(b1, show = "genotypes", type = "stream")
## ---- fig.width=6-------------------------------------------------
set.seed(678)
nd <- 70
np <- 5000
s <- 0.1
sp <- 1e-3
spp <- -sp/(1 + sp)
mcf1 <- allFitnessEffects(noIntGenes = c(rep(s, nd), rep(spp, np)),
drvNames = seq.int(nd))
mcf1s <- oncoSimulIndiv(mcf1,
model = "McFL",
mu = 1e-7,
detectionProb = "default",
detectionSize = NA,
detectionDrivers = NA,
sampleEvery = 0.025,
keepEvery = 8,
initSize = 2000,
finalTime = 4000,
onlyCancer = FALSE)
summary(mcf1s)
## ----mcf1sx1,fig.width=6.5, fig.height=10-------------------------
par(mfrow = c(2, 1))
## I use thinData to make figures smaller and faster
plot(mcf1s, addtot = TRUE, lwdClone = 0.9, log = "",
thinData = TRUE, thinData.keep = 0.5)
plot(mcf1s, show = "drivers", type = "stacked",
thinData = TRUE, thinData.keep = 0.3,
legend.ncols = 2)
## ---- eval=FALSE--------------------------------------------------
#
# set.seed(123)
# nd <- 70
# np <- 50000
# s <- 0.1
# sp <- 1e-4 ## as we have many more passengers
# spp <- -sp/(1 + sp)
# mcfL <- allFitnessEffects(noIntGenes = c(rep(s, nd), rep(spp, np)),
# drvNames = seq.int(nd))
# mcfLs <- oncoSimulIndiv(mcfL,
# model = "McFL",
# mu = 1e-7,
# detectionSize = 1e8,
# detectionDrivers = 100,
# sampleEvery = 0.02,
# keepEvery = 2,
# initSize = 1000,
# finalTime = 2000,
# onlyCancer = FALSE)
## ---- mcflsx2,fig.width=6-----------------------------------------
data(mcfLs)
plot(mcfLs, addtot = TRUE, lwdClone = 0.9, log = "",
thinData = TRUE, thinData.keep = 0.3,
plotDiversity = TRUE)
## -----------------------------------------------------------------
summary(mcfLs)
## number of passengers per clone
summary(colSums(mcfLs$Genotypes[-(1:70), ]))
## ----mcflsx3------------------------------------------------------
plot(mcfLs, type = "stacked", thinData = TRUE,
thinData.keep = 0.1,
plotDiversity = TRUE,
xlim = c(0, 1000))
## -----------------------------------------------------------------
data(examplesFitnessEffects)
names(examplesFitnessEffects)
## ----seedsmmmcfls-------------------------------------------------
set.seed(1)
## ----smmcfls------------------------------------------------------
data(examplesFitnessEffects)
evalAllGenotypes(examplesFitnessEffects$cbn1, order = FALSE)[1:10, ]
sm <- oncoSimulIndiv(examplesFitnessEffects$cbn1,
model = "McFL",
mu = 5e-7,
detectionSize = 1e8,
detectionDrivers = 2,
detectionProb = "default",
sampleEvery = 0.025,
keepEvery = 5,
initSize = 2000,
onlyCancer = TRUE)
summary(sm)
## ----smbosb1------------------------------------------------------
set.seed(1234)
evalAllGenotypes(examplesFitnessEffects$cbn1, order = FALSE,
model = "Bozic")[1:10, ]
sb <- oncoSimulIndiv(examplesFitnessEffects$cbn1,
model = "Bozic",
mu = 5e-6,
detectionProb = "default",
detectionSize = 1e8,
detectionDrivers = 4,
sampleEvery = 2,
initSize = 2000,
onlyCancer = TRUE)
summary(sb)
## ----sbx1,fig.width=6.5, fig.height=3.3---------------------------
## Show drivers, line plot
par(cex = 0.75, las = 1)
plot(sb,show = "drivers", type = "line", addtot = TRUE,
plotDiversity = TRUE)
## ----sbx2,fig.width=6.5, fig.height=3.3---------------------------
## Drivers, stacked
par(cex = 0.75, las = 1)
plot(sb,show = "drivers", type = "stacked", plotDiversity = TRUE)
## ----sbx3,fig.width=6.5, fig.height=3.3---------------------------
## Drivers, stream
par(cex = 0.75, las = 1)
plot(sb,show = "drivers", type = "stream", plotDiversity = TRUE)
## ----sbx4,fig.width=6.5, fig.height=3.3---------------------------
## Genotypes, line plot
par(cex = 0.75, las = 1)
plot(sb,show = "genotypes", type = "line", plotDiversity = TRUE)
## ----sbx5,fig.width=6.5, fig.height=3.3---------------------------
## Genotypes, stacked
par(cex = 0.75, las = 1)
plot(sb,show = "genotypes", type = "stacked", plotDiversity = TRUE)
## ----sbx6,fig.width=6.5, fig.height=3.3---------------------------
## Genotypes, stream
par(cex = 0.75, las = 1)
plot(sb,show = "genotypes", type = "stream", plotDiversity = TRUE)
## ---- fig.width=6-------------------------------------------------
set.seed(4321)
tmp <- oncoSimulIndiv(examplesFitnessEffects[["o3"]],
model = "McFL",
mu = 5e-5,
detectionSize = 1e8,
detectionDrivers = 3,
sampleEvery = 0.025,
max.num.tries = 10,
keepEvery = 5,
initSize = 2000,
finalTime = 6000,
onlyCancer = FALSE)
## ----tmpmx1,fig.width=6.5, fig.height=4.1-------------------------
par(las = 1, cex = 0.85)
plot(tmp, addtot = TRUE, log = "", plotDiversity = TRUE,
thinData = TRUE, thinData.keep = 0.2)
## ----tmpmx2,fig.width=6.5, fig.height=4.1-------------------------
par(las = 1, cex = 0.85)
plot(tmp, type = "stacked", plotDiversity = TRUE,
ylim = c(0, 5500), legend.ncols = 4,
thinData = TRUE, thinData.keep = 0.2)
## -----------------------------------------------------------------
evalAllGenotypes(examplesFitnessEffects[["o3"]], addwt = TRUE,
order = TRUE)
## ----tmpmx3,fig.width=6.5, fig.height=5.5-------------------------
plot(tmp, show = "genotypes", ylim = c(0, 5500), legend.ncols = 3,
thinData = TRUE, thinData.keep = 0.5)
## -----------------------------------------------------------------
set.seed(15)
tmp <- oncoSimulIndiv(examplesFitnessEffects[["o3"]],
model = "McFL",
mu = 5e-5,
detectionSize = 1e8,
detectionDrivers = 3,
sampleEvery = 0.025,
max.num.tries = 10,
keepEvery = 5,
initSize = 2000,
finalTime = 20000,
onlyCancer = FALSE,
extraTime = 1500)
tmp
## ----tmpmdx5,fig.width=6.5, fig.height=4--------------------------
par(las = 1, cex = 0.85)
plot(tmp, addtot = TRUE, log = "", plotDiversity = TRUE,
thinData = TRUE, thinData.keep = 0.5)
## ----tmpmdx6,fig.width=6.5, fig.height=4--------------------------
par(las = 1, cex = 0.85)
plot(tmp, type = "stacked", plotDiversity = TRUE,
legend.ncols = 4, ylim = c(0, 5200), xlim = c(3400, 5000),
thinData = TRUE, thinData.keep = 0.5)
## ----tmpmdx7,fig.width=6.5, fig.height=5.3------------------------
## Improve telling apart the most abundant
## genotypes by sorting colors
## differently via breakSortColors
## Modify ncols of legend, so it is legible by not overlapping
## with plot
par(las = 1, cex = 0.85)
plot(tmp, show = "genotypes", breakSortColors = "distave",
plotDiversity = TRUE, legend.ncols = 4,
ylim = c(0, 5300), xlim = c(3400, 5000),
thinData = TRUE, thinData.keep = 0.5)
## ---- eval=FALSE--------------------------------------------------
# ## Convert the data
# lb1 <- OncoSimulWide2Long(b1)
#
# ## Install the streamgraph package from GitHub and load
# library(devtools)
# devtools::install_github("hrbrmstr/streamgraph")
# library(streamgraph)
#
# ## Stream plot for Genotypes
# sg_legend(streamgraph(lb1, Genotype, Y, Time, scale = "continuous"),
# show=TRUE, label="Genotype: ")
#
# ## Staked area plot and we use the pipe
# streamgraph(lb1, Genotype, Y, Time, scale = "continuous",
# offset = "zero") %>%
# sg_legend(show=TRUE, label="Genotype: ")
## ----minitm1------------------------------------------------------
r2 <- rfitness(6)
## Make sure these always viable for interesting stuff
r2[2, 7] <- 1 + runif(1) # A
r2[4, 7] <- 1 + runif(1) # C
r2[8, 7] <- 1 + runif(1) # A, B
o2 <- allFitnessEffects(genotFitness = r2)
ag <- evalAllGenotypes(o2)
out1 <- oncoSimulIndiv(o2, initMutant = c("A", "C"),
initSize = c(100, 200),
onlyCancer = FALSE,
finalTime = 200)
## ----minitm1fdf---------------------------------------------------
gffd0 <- data.frame(
Genotype = c(
"A", "A, B",
"C", "C, D", "C, E"),
Fitness = c(
"1.3",
"1.4",
"1.4",
"1.1 + 0.7*((f_A + f_A_B) > 0.3)",
"1.2 + sqrt(f_A + f_C + f_C_D)"))
afd0 <- allFitnessEffects(genotFitness = gffd0,
frequencyDependentFitness = TRUE)
sp <- 1:5
names(sp) <- c("A", "C", "A, B", "C, D", "C, E")
eag0 <- evalAllGenotypes(afd0, spPopSizes = sp)
os0 <- oncoSimulIndiv(afd0,
initMutant = c("A", "C"),
finalTime = 20, initSize = c(1e4, 1e5),
onlyCancer = FALSE, model = "McFLD")
## ----mspeci1------------------------------------------------------
mspec <- data.frame(
Genotype = c("A",
"A, a1", "A, a2", "A, a1, a2",
"B",
"B, b1", "B, b2", "B, b3",
"B, b1, b2", "B, b1, b3", "B, b1, b2, b3"),
Fitness = 1 + runif(11)
)
fmspec <- allFitnessEffects(genotFitness = mspec)
afmspec <- evalAllGenotypes(fmspec)
## Show only viable ones
afmspec[afmspec$Fitness >= 1, ]
muv <- c(1e-10, rep(1e-5, 2), 1e-10, rep(1e-5, 3))
names(muv) <- c("A", paste0("a", 1:2), "B", paste0("b", 1:3))
out1 <- oncoSimulIndiv(fmspec, initMutant = c("A", "B"),
initSize = c(100, 200),
mu = muv,
onlyCancer = FALSE,
finalTime = 200)
## ----mspeci2------------------------------------------------------
mspecF <- data.frame(
Genotype = c("A",
"A, a1", "A, a2", "A, a1, a2",
"B",
"B, b1", "B, b2", "B, b3",
"B, b1, b2", "B, b1, b3", "B, b1, b2, b3"),
Fitness = c("1 + f_A_a1",
"1 + f_A_a2",
"1 + f_A_a1_a2",
"1 + f_B",
"1 + f_B_b1",
"1 + f_B_b2",
"1 + f_B_b3",
"1 + f_B_b1_b2",
"1 + f_B_b1_b3",
"1 + f_B_b1_b2_b3",
"1 + f_A")
)
fmspecF <- allFitnessEffects(genotFitness = mspecF,
frequencyDependentFitness = TRUE)
## Remeber, spPopSizes correspond to the genotypes
## shown in
fmspecF$full_FDF_spec
## in exactly that order if it is unnamed.
afmspecF <- evalAllGenotypes(fmspecF,
spPopSizes = 1:11)
## Alternatively, pass a named vector, which is the recommended approach
spp <- 1:11
names(spp) <- c("A","B",
"A, a1", "A, a2",
"B, b1", "B, b2", "B, b3",
"A, a1, a2",
"B, b1, b2", "B, b1, b3", "B, b1, b2, b3")
afmspecF <- evalAllGenotypes(fmspecF,
spPopSizes = spp)
## Show only viable ones
afmspecF[afmspecF$Fitness >= 1, ]
## Expected values of fitness
exv <- 1 + c(3, 5, 4, 8, 6, 7, 9, 2, 10, 11, 1)/sum(1:11)
stopifnot(isTRUE(all.equal(exv, afmspecF[afmspecF$Fitness >= 1, ]$Fitness)))
muv <- c(1e-10, rep(1e-5, 2), 1e-10, rep(1e-5, 3))
names(muv) <- c("A", paste0("a", 1:2), "B", paste0("b", 1:3))
out1 <- oncoSimulIndiv(fmspecF, initMutant = c("A", "B"),
initSize = c(1e4, 1e5),
mu = muv,
finalTime = 20,
model = "McFLD",
onlyCancer = FALSE)
## ----pancrpopcreate-----------------------------------------------
pancrPop <- oncoSimulPop(4, pancr,
detectionSize = 1e7,
keepEvery = 10,
mc.cores = 2)
summary(pancrPop)
samplePop(pancrPop)
## -----------------------------------------------------------------
library(parallel)
if(.Platform$OS.type == "windows") {
mc.cores <- 1
} else {
mc.cores <- 2
}
p2 <- mclapply(1:4, function(x) oncoSimulIndiv(pancr,
detectionSize = 1e7,
keepEvery = 10),
mc.cores = mc.cores)
class(p2) <- "oncosimulpop"
samplePop(p2)
## -----------------------------------------------------------------
tail(pancrPop[[1]]$pops.by.time)
## -----------------------------------------------------------------
pancrPopNH <- oncoSimulPop(4, pancr,
detectionSize = 1e7,
keepEvery = NA,
mc.cores = 2)
summary(pancrPopNH)
samplePop(pancrPopNH)
## -----------------------------------------------------------------
pancrPopNH[[1]]$pops.by.time
## -----------------------------------------------------------------
pancrSamp <- oncoSimulSample(4, pancr)
pancrSamp$popSamp
## -----------------------------------------------------------------
set.seed(15)
tmp <- oncoSimulIndiv(examplesFitnessEffects[["o3"]],
model = "McFL",
mu = 5e-5,
detectionSize = 1e8,
detectionDrivers = 3,
sampleEvery = 0.025,
max.num.tries = 10,
keepEvery = 5,
initSize = 2000,
finalTime = 20000,
onlyCancer = FALSE,
extraTime = 1500,
keepPhylog = TRUE)
tmp
## -----------------------------------------------------------------
plotClonePhylog(tmp, N = 0)
## -----------------------------------------------------------------
plotClonePhylog(tmp, N = 1)
## ----pcpkeepx1----------------------------------------------------
plotClonePhylog(tmp, N = 1, keepEvents = TRUE)
## -----------------------------------------------------------------
plotClonePhylog(tmp, N = 1, timeEvents = TRUE)
## ---- fig.keep="none"---------------------------------------------
get.adjacency(plotClonePhylog(tmp, N = 1, returnGraph = TRUE))
## -----------------------------------------------------------------
set.seed(456)
mcf1s <- oncoSimulIndiv(mcf1,
model = "McFL",
mu = 1e-7,
detectionSize = 1e8,
detectionDrivers = 100,
sampleEvery = 0.025,
keepEvery = 2,
initSize = 2000,
finalTime = 1000,
onlyCancer = FALSE,
keepPhylog = TRUE)
## -----------------------------------------------------------------
plotClonePhylog(mcf1s, N = 1)
## -----------------------------------------------------------------
par(cex = 0.7)
plotClonePhylog(mcf1s, N = 1, timeEvents = TRUE)
## -----------------------------------------------------------------
par(cex = 0.7)
plotClonePhylog(mcf1s, N = 1, t = c(800, 1000))
## -----------------------------------------------------------------
par(cex = 0.7)
plotClonePhylog(mcf1s, N = 1, t = c(900, 1000), timeEvents = TRUE)
## ----fig.keep="none"----------------------------------------------
g1 <- plotClonePhylog(mcf1s, N = 1, t = c(900, 1000),
returnGraph = TRUE)
## -----------------------------------------------------------------
plot(g1)
## ---- eval=FALSE--------------------------------------------------
# op <- par(ask = TRUE)
# while(TRUE) {
# tmp <- oncoSimulIndiv(smn1, model = "McFL",
# mu = 5e-5, finalTime = 500,
# detectionDrivers = 3,
# onlyCancer = FALSE,
# initSize = 1000, keepPhylog = TRUE)
# plotClonePhylog(tmp, N = 0)
# }
# par(op)
## -----------------------------------------------------------------
oi <- allFitnessEffects(orderEffects =
c("F > D" = -0.3, "D > F" = 0.4),
noIntGenes = rexp(5, 10),
geneToModule =
c("F" = "f1, f2, f3",
"D" = "d1, d2") )
oiI1 <- oncoSimulIndiv(oi, model = "Exp")
oiP1 <- oncoSimulPop(4, oi,
keepEvery = 10,
mc.cores = 2,
keepPhylog = TRUE)
## ---- fig.height=9------------------------------------------------
op <- par(mar = rep(0, 4), mfrow = c(2, 1))
plotClonePhylog(oiP1[[1]])
plotClonePhylog(oiP1[[2]])
par(op)
## -----------------------------------------------------------------
## A small example
rfitness(3)
## A 5-gene example, where the reference genotype is the
## one with all positions mutated, similar to Greene and Crona,
## 2014. We will plot the landscape and use it for simulations
## We downplay the random component with a sd = 0.5
r1 <- rfitness(5, reference = rep(1, 5), sd = 0.6)
plot(r1)
oncoSimulIndiv(allFitnessEffects(genotFitness = r1))
## ----nkex1--------------------------------------------------------
rnk <- rfitness(5, K = 3, model = "NK")
plot(rnk)
oncoSimulIndiv(allFitnessEffects(genotFitness = rnk))
## ----addex1-------------------------------------------------------
radd <- rfitness(4, model = "Additive", mu = 0, sd = 0.5)
plot(radd)
## ----eggex1-------------------------------------------------------
regg <- rfitness(4, model = "Eggbox", e = 1, E = 0.5)
plot(regg)
## ----isingex1-----------------------------------------------------
ris <- rfitness(g = 4, model = "Ising", i = 0.002, I = 0.45)
plot(ris)
## ----fullex1------------------------------------------------------
rnk <- rfitness(4, model = "Full", i = 0.5, I = 0.1,
e = 2, s = 0.3, S = 0.08)
plot(rnk)
## ----magstats1----------------------------------------------------
rnk1 <- rfitness(6, K = 1, model = "NK")
Magellan_stats(rnk1)
rnk2 <- rfitness(6, K = 4, model = "NK")
Magellan_stats(rnk2)
## ----fdf1---------------------------------------------------------
## Define fitness of the different genotypes
gffd <- data.frame(
Genotype = c("WT", "A", "B", "C", "A, B"),
Fitness = c("1 + 1.5 * f_A_B",
"1.3 + 1.5 * f_A_B",
"1.4",
"1.1 + 0.7*((f_A + f_B) > 0.3) + f_A_B",
"1.2 + sqrt(f_1 + f_C + f_B) - 0.3 * (f_A_B > 0.5)"))
## ----fdf1named----------------------------------------------------
## Define fitness of the different genotypes
gffdn <- data.frame(
Genotype = c("WT", "A", "B", "C", "A, B"),
Fitness = c("1 + 1.5 * f_1_2",
"1.3 + 1.5 * f_1_2",
"1.4",
"1.1 + 0.7*((f_1 + f_2) > 0.3) + f_1_2",
"1.2 + sqrt(f_1 + f_3 + f_2) - 0.3 * (f_1_2 > 0.5)"),
stringsAsFactors = FALSE)
## ----fdf1b--------------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness = gffd,
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(WT = 100, A = 20, B = 20, C = 30, "A, B" = 0))
## Notice the warning
evalAllGenotypes(allFitnessEffects(genotFitness = gffd,
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(100, 30, 40, 0, 10))
evalAllGenotypes(allFitnessEffects(genotFitness = gffd,
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(100, 30, 40, 0, 100))
## ----fdf1bnamed---------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness = gffdn,
frequencyDependentFitness = TRUE),
spPopSizes = c(100, 20, 20, 30, 0))
evalAllGenotypes(allFitnessEffects(genotFitness = gffdn,
frequencyDependentFitness = TRUE),
spPopSizes = c(100, 30, 40, 0, 10))
evalAllGenotypes(allFitnessEffects(genotFitness = gffdn,
frequencyDependentFitness = TRUE),
spPopSizes = c(100, 30, 40, 0, 100))
## ----fdf1c--------------------------------------------------------
afd <- allFitnessEffects(genotFitness = gffd,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(1) ## for reproducibility
sfd <- oncoSimulIndiv(afd,
model = "McFL",
onlyCancer = FALSE,
finalTime = 55, ## short, for speed
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(sfd, show = "genotypes")
## ----hurlbutpay, eval=TRUE,echo=FALSE, fig.cap="Payoff matrix from Table 2 of Hurlbut et al., 2018, 'Game Theoretical Model of Cancer Dynamics withFour Cell Phenotypes', *Games*, 9, 61; doi:10.3390/g9030061."----
knitr::include_graphics("hurlbut.png")
## ----hurlbutfit1--------------------------------------------------
create_fe <- function(a, b, c, d, e, f, g,
gt = c("WT", "A", "P", "C")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ",
d, " * f_A ",
"- ", c, " * f_C"),
paste0("1 - ", a,
" + ", d, " + ",
f, " * f_A ",
"- ", c, " * f_C"),
paste0("1 + ", g, " + ",
d, " * f_A ",
"- ", c, " * (1 + ",
g, ") * f_C"),
paste0("1 - ", b, " + ",
e, " * f_ + ",
"(", d, " + ",
e, ") * f_A + ",
e , " * f_P")))
}
## ----hbf1check----------------------------------------------------
create_fe("a", "b", "c", "d", "e", "f", "g")
## ----hurlbutfit2--------------------------------------------------
## Different assumption about origins from mutation:
## WT -> P; P -> A,P; P -> C,P
create_fe2 <- function(a, b, c, d, e, f, g,
gt = c("WT", "A", "P", "C", "A, P", "A, C",
"C, P")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ",
d, " * f_A_P ",
"- ", c, " * f_P_C"),
"0",
paste0("1 + ", g, " + ",
d, " * f_A_P ",
"- ", c, " * (1 + ",
g, ") * f_P_C"),
"0",
paste0("1 - ", a, " + ",
d, " + ",
f, " * f_A_P ",
"- ", c, " * f_P_C"),
"0",
paste0("1 - ", b, " + ",
e, " * f_ + ",
"(", d, " + ",
e, ") * f_A_P + ",
e , " * f_P")),
stringsAsFactors = FALSE)
}
## And check:
create_fe2("a", "b", "c", "d", "e", "f", "g")
## ----hurl3a, message=FALSE----------------------------------------
## Figure 3a
afe_3_a <- allFitnessEffects(
genotFitness =
create_fe(0.02, 0.04, 0.08, 0.06,
0.15, 0.1, 0.06),
frequencyDependentFitness = TRUE)
set.seed(2)
s_3_a <- oncoSimulIndiv(afe_3_a,
model = "McFL",
onlyCancer = FALSE,
finalTime = 160,
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## plot(s_3_a, show = "genotypes",
## xlim = c(40, 200),
## col = c("black", "green", "red", "blue"))
plot(s_3_a, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue"),
thinData = TRUE)
## ----hurl3b, message=FALSE----------------------------------------
## Figure 3b
afe_3_b <- allFitnessEffects(
genotFitness =
create_fe(0.02, 0.04, 0.08, 0.1,
0.15, 0.1, 0.05),
frequencyDependentFitness = TRUE)
set.seed(2)
## Use a short finalTime, for speed of vignette execution
s_3_b <- oncoSimulIndiv(afe_3_b,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100, ## 160,
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## plot(s_3_b, show = "genotypes",
## col = c("black", "green", "red", "blue"))
plot(s_3_b, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue"),
thinData = TRUE) ## thin for faster plotting
## ----hurl3b2------------------------------------------------------
## Figure 3b. Now with WT -> P; P -> A,P; P -> C,P
## For speed, we set finalTiem = 100
afe_3_b_2 <- allFitnessEffects(
genotFitness =
create_fe2(0.02, 0.04, 0.08, 0.1,
0.15, 0.1, 0.05),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(2)
s_3_b_2 <- oncoSimulIndiv(afe_3_b_2,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100, ## 300
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s_3_b_2, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue"),
thinData = TRUE)
## ----fdf2, message=FALSE------------------------------------------
gffd3 <- data.frame(Genotype = c("WT", "A", "B"),
Fitness = c("1",
"1 + 0.2 * (n_B > 10)",
".9 + 0.4 * (n_A > 10)"
))
afd3 <- allFitnessEffects(genotFitness = gffd3,
frequencyDependentFitness = TRUE)
## ----fdf2b, message=FALSE-----------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness = gffd3,
frequencyDependentFitness = TRUE),
spPopSizes = c(WT = 100, A = 1, B = 11))
evalAllGenotypes(allFitnessEffects(genotFitness = gffd3,
frequencyDependentFitness = TRUE),
spPopSizes = c(WT = 100, A = 11, B = 1))
## ----fdf2c--------------------------------------------------------
set.seed(1)
sfd3 <- oncoSimulIndiv(afd3,
model = "McFLD",
onlyCancer = FALSE,
finalTime = 200,
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----echo=FALSE---------------------------------------------------
op <- par(mfrow = c(1, 2))
## -----------------------------------------------------------------
plot(sfd3, show = "genotypes", type = "line")
plot(sfd3, show = "genotypes")
sfd3
## ----echo=FALSE---------------------------------------------------
par(op)
## ----fdf2d--------------------------------------------------------
set.seed(1)
sfd4 <- oncoSimulIndiv(afd3,
model = "McFL",
onlyCancer = FALSE,
finalTime = 145,
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ---- echo=FALSE--------------------------------------------------
op <- par(mfrow = c(1, 2))
## ----polotfdfv6---------------------------------------------------
plot(sfd4, show = "genotypes", type = "line")
plot(sfd4, show = "genotypes")
sfd4
## ---- echo=FALSE--------------------------------------------------
par(op)
## ----fdfpopfinal--------------------------------------------------
## Check final pop size corresponds to birth = death
K <- 5000/(exp(1) - 1)
K
log1p(4290/K)
## ----lotka1-------------------------------------------------------
G_fe_LV <- function(r1, r2, K1, K2, a_12, a_21, awt = 1e-4,
gt = c("WT", "S1", "S2")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("max(0.1, 1 - ", awt, " * (n_2 + n_1))"),
paste0("1 + ", r1,
" * ( 1 - (n_1 + ", a_12, " * n_2)/", K1,
")"),
paste0("1 + ", r2,
" * ( 1 - (n_2 + ", a_21, " * n_1)/", K2,
")")
))
}
## Show expressions for birth rates
G_fe_LV("r1", "r2", "K1", "K2", "a_12", "a_21", "awt")
## ---- echo = FALSE------------------------------------------------
set.seed(1)
## ----complv1, message=FALSE---------------------------------------
fe_competition <-
allFitnessEffects(
genotFitness =
G_fe_LV(1.5, 1.4, 10000, 4000, 0.6, 0.2,
gt = c("WT","S1", "S2")),
frequencyDependentFitness = TRUE,
frequencyType = "abs")
competition <- oncoSimulIndiv(fe_competition,
model = "Exp",
onlyCancer = FALSE,
finalTime = 100,
mu = 1e-4,
initSize = 40000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----pp1wt--------------------------------------------------------
plot(competition, show = "genotypes")
## ---- echo=FALSE--------------------------------------------------
op <- par(mfrow = c(1, 2))
## ----pp1nowt------------------------------------------------------
plot(competition, show = "genotypes",
xlim = c(80, 100))
plot(competition, show = "genotypes", type = "line",
xlim = c(80, 100), ylim = c(1500, 12000))
## ---- echo=FALSE--------------------------------------------------
par(op)
## ----lotka1multi--------------------------------------------------
G_fe_LVm <- function(r1, r2, K1, K2, a_12, a_21, awt = 1e-4,
gt = c("S1", "S2")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ", r1,
" * ( 1 - (n_1 + ", a_12, " * n_2)/", K1,
")"),
paste0("1 + ", r2,
" * ( 1 - (n_2 + ", a_21, " * n_1)/", K2,
")")
))
}
## Show expressions for birth rates
G_fe_LVm("r1", "r2", "K1", "K2", "a_12", "a_21", "awt")
## ---- echo = FALSE------------------------------------------------
set.seed(1)
## ----complv1multi, message=FALSE----------------------------------
fe_competitionm <-
allFitnessEffects(
genotFitness =
G_fe_LVm(1.5, 1.4, 10000, 4000, 0.6, 0.2,
gt = c("S1", "S2")),
frequencyDependentFitness = TRUE)
fe_competitionm$full_FDF_spec
competitionm <- oncoSimulIndiv(fe_competitionm,
model = "Exp",
initMutant = c("S1", "S2"),
initSize = c(5000, 2000),
onlyCancer = FALSE,
finalTime = 100,
mu = 1e-4,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----pp1wtmulti---------------------------------------------------
plot(competitionm, show = "genotypes")
## ----ppreydefvm2--------------------------------------------------
G_fe_LVm2 <- function(r1, r2, K1, K2, a_12, a_21, awt = 1e-4,
gt = c("S1", "S2")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ", r1,
" * ( 1 - (n_", gt[1], " + ", a_12, " * n_", gt[2], ")/", K1,
")"),
paste0("1 + ", r2,
" * ( 1 - (n_", gt[2], " + ", a_21, " * n_", gt[1], ")/", K2,
")")
))
}
## But notice that, because of ordering, "prey" ends up being n_2
## but that is not a problem.
fe_pred_preym2 <-
allFitnessEffects(
genotFitness =
G_fe_LVm2(1.5, 1.4, 10000, 4000, 1.1, -0.5, awt = 1,
gt = c("prey", "Predator")),
frequencyDependentFitness = TRUE)
fe_pred_preym2$full_FDF_spec
## Change order and note how these are, of course, equivalent
fe_pred_preym3 <-
allFitnessEffects(
genotFitness =
G_fe_LVm2(1.4, 1.5, 4000, 10000, -0.5, 1.1, awt = 1,
gt = c("Predator", "prey")),
frequencyDependentFitness = TRUE)
fe_pred_preym3$full_FDF_spec
evalAllGenotypes(fe_pred_preym2, spPopSizes = c(1000, 300))
evalAllGenotypes(fe_pred_preym3, spPopSizes = c(300, 1000))
## ---- echo=FALSE--------------------------------------------------
set.seed(1)
## ----pprey3-------------------------------------------------------
s_pred_preym2 <- oncoSimulIndiv(fe_pred_preym2,
model = "Exp",
initMutant = c("prey", "Predator"),
initSize = c(1000, 1000),
onlyCancer = FALSE,
finalTime = 200,
mu = 1e-3,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----prepreylv1237------------------------------------------------
plot(s_pred_preym2, show = "genotypes")
## ----prepreylv1238------------------------------------------------
evalAllGenotypes(fe_pred_preym2, spPopSizes = c(0, 300))
evalAllGenotypes(allFitnessEffects(
genotFitness =
G_fe_LVm2(1.5, 1.4, 100, 40,
0.6, -0.5, awt = 0.1,
gt = c("prey", "Predator")),
frequencyDependentFitness = TRUE),
spPopSizes = c(0, 40))
## ----predprey2a---------------------------------------------------
C_fe_pred_prey2 <- function(r, a, c, e, d,
gt = c("s1", "s2")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ", r, " - ", a,
" * ", c, " * n_2"),
paste0("1 + ", e, " * ", a,
" * ", c, " * n_1 - ", d)
))
}
C_fe_pred_prey2("r", "a", "c", "e", "d")
## ----echo=FALSE---------------------------------------------------
set.seed(2)
## ----predprey2b---------------------------------------------------
fe_pred_prey2 <-
allFitnessEffects(
genotFitness =
C_fe_pred_prey2(r = .7, a = 1, c = 0.005,
e = 0.02, d = 0.4,
gt = c("Fly", "Lizard")),
frequencyDependentFitness = TRUE)
fe_pred_prey2$full_FDF_spec
## You want to make sure you start the simulation from
## a viable condition
evalAllGenotypes(fe_pred_prey2,
spPopSizes = c(5000, 100))
set.seed(2)
pred_prey2 <- oncoSimulIndiv(fe_pred_prey2,
model = "Exp",
initMutant = c("Fly", "Lizard"),
initSize = c(500, 100),
sampleEvery = 0.1,
mu = 1e-3,
onlyCancer = FALSE,
finalTime = 100,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
op <- par(mfrow = c(1, 2))
## Nicer colors
plot(pred_prey2, show = "genotypes")
## But this shows better what is going on
plot(pred_prey2, show = "genotypes", type = "line")
par(op)
## ----commens, eval=FALSE------------------------------------------
# fe_commens <-
# allFitnessEffects(
# genotFitness =
# G_fe_LV(1.2, 1.3, 5000, 20000,
# 0, -0.2,
# gt = c("WT","A", "Commensal")),
# frequencyDependentFitness = TRUE,
# frequencyType = "abs")
#
# commens <- oncoSimulIndiv(fe_commens,
# model = "Exp",
# onlyCancer = FALSE,
# finalTime = 100,
# mu = 1e-4,
# initSize = 40000,
# keepPhylog = TRUE,
# seed = NULL,
# errorHitMaxTries = FALSE,
# errorHitWallTime = FALSE)
#
# plot(commens, show = "genotypes")
#
# plot(commens, show = "genotypes",
# xlim = c(80, 100))
#
# plot(commens, show = "genotypes", type = "line",
# xlim = c(80, 100), ylim = c(2000, 22000))
#
## ----fdfar, message=FALSE-----------------------------------------
rar <- data.frame(Genotype = c("WT", "A", "B", "C"),
Fitness = c("1",
"1.1 + .3*f_2",
"1.2 + .4*f_1",
"1.0 + .5 * (f_1 + f_2)"))
afear <- allFitnessEffects(genotFitness = rar,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
evalAllGenotypes(afear, spPopSizes = c(100, 200, 300, 400))
rar2 <- data.frame(Genotype = c("WT", "A", "B", "C"),
Fitness = c("1",
"1.1 + .3*(n_2/N)",
"1.2 + .4*(n_1/N)",
"1.0 + .5 * ((n_1 + n_2)/N)"))
afear2 <- allFitnessEffects(genotFitness = rar2,
frequencyDependentFitness = TRUE,
frequencyType = "abs")
evalAllGenotypes(afear2, spPopSizes = c(100, 200, 300, 400))
## ----relarres, message=FALSE--------------------------------------
set.seed(1)
tmp1 <- oncoSimulIndiv(afear,
model = "McFL",
onlyCancer = FALSE,
finalTime = 30,
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
set.seed(1)
tmp2 <- oncoSimulIndiv(afear2,
model = "McFL",
onlyCancer = FALSE,
finalTime = 30,
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
stopifnot(identical(print(tmp1), print(tmp2)))
## ----relar3a, message=FALSE---------------------------------------
rar3 <- data.frame(Genotype = c("WT", "A", "B", "C"),
Fitness = c("1",
"1.1 + .3*(n_2/N)",
"1.2 + .4*(n_1/N)",
"1.0 + .5 * ( n_1 > 20)"))
afear3 <- allFitnessEffects(genotFitness = rar3,
frequencyDependentFitness = TRUE,
frequencyType = "abs")
evalAllGenotypes(afear3, spPopSizes = c(100, 200, 300, 400))
set.seed(1)
tmp3 <- oncoSimulIndiv(afear3,
model = "McFL",
onlyCancer = FALSE,
finalTime = 60,
mu = 1e-4,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(tmp3, show = "genotypes")
## ----fdfmutex-----------------------------------------------------
## Relative
r1fd <- data.frame(Genotype = c("WT", "A", "B", "A, B"),
Fitness = c("1",
"1.4 + 1*(f_2)",
"1.4 + 1*(f_1)",
"1.6 + f_1 + f_2"))
afe4 <- allFitnessEffects(genotFitness = r1fd,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(1)
s1fd <- oncoSimulIndiv(afe4,
model = "McFL",
onlyCancer = FALSE,
finalTime = 40,
mu = 1e-4,
initSize = 5000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s1fd, show = "genotypes")
mtfd <- allMutatorEffects(epistasis = c("A" = 0.1,
"B" = 10))
set.seed(1)
s2fd <- oncoSimulIndiv(afe4,
muEF = mtfd,
model = "McFL",
onlyCancer = FALSE,
finalTime = 40,
mu = 1e-4,
initSize = 5000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s2fd, show = "genotypes")
## ----echo=FALSE---------------------------------------------------
op <- par(mfrow = c(1, 2))
## ----figmutfdf----------------------------------------------------
plotClonePhylog(s1fd, keepEvents = TRUE)
plotClonePhylog(s2fd, keepEvents = TRUE)
## ----echo=FALSE---------------------------------------------------
par(op)
## ----exmutfdf2, eval=FALSE----------------------------------------
#
# ## Absolute
# r5 <- data.frame(Genotype = c("WT", "A", "B", "A, B"),
# Fitness = c("1",
# "1.25 - .0025*(n_2)",
# "1.25 - .0025*(n_1)",
# "1.4"),
# stringsAsFactors = FALSE)
#
# afe5 <- allFitnessEffects(genotFitness = r5,
# frequencyDependentFitness = TRUE,
# frequencyType = "abs")
# set.seed(8)
# s5 <- oncoSimulIndiv(afe5,
# model = "McFL",
# onlyCancer = FALSE,
# finalTime = 100,
# mu = 1e-4,
# initSize = 5000,
# keepPhylog = TRUE,
# seed = NULL,
# errorHitMaxTries = FALSE,
# errorHitWallTime = FALSE)
# plot(s5, show = "genotypes")
# plot(s5, show = "genotypes", log = "y", type = "line")
#
# mt <- allMutatorEffects(epistasis = c("A" = 0.1,
# "B" = 10))
# set.seed(8)
# s6 <- oncoSimulIndiv(afe5,
# muEF = mt,
# model = "McFL",
# onlyCancer = FALSE,
# finalTime = 100,
# mu = 1e-4,
# initSize = 5000,
# keepPhylog = TRUE,
# seed = NULL,
# errorHitMaxTries = FALSE,
# errorHitWallTime = FALSE)
# plot(s6, show = "genotypes")
# plot(s6, show = "genotypes", log = "y", type = "line")
#
# plotClonePhylog(s5, keepEvents = TRUE)
# plotClonePhylog(s6, keepEvents = TRUE)
#
## ----noworkeval---------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness = r1fd,
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(10, 20, 30, 40))
evalAllGenotypesFitAndMut(allFitnessEffects(genotFitness = r1fd,
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
mtfd,
spPopSizes = c(10, 20, 30, 40))
## ----rps1, message=F---------------------------------------------
crs <- function (a, b, c){
data.frame(Genotype = c("WT", "C", "R"),
Fitness = c(paste0("1 + ", a, " * f_R - ", b, " * f_C"),
paste0("1 + ", b, " * f_ - ", c, " * f_R"),
paste0("1 + ", c, " * f_C - ", a, " * f_")
))
}
## ----rps2, message=F----------------------------------------------
crs("a", "b", "c")
## ----sps3b, message=F---------------------------------------------
afcrs1 <- allFitnessEffects(genotFitness = crs(1, 1, 1),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
resultscrs1 <- oncoSimulIndiv(afcrs1,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100,
mu = 1e-2,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
op <- par(mfrow = c(1, 2))
plot(resultscrs1, show = "genotypes", type = "line", cex.lab=1.1,
las = 1)
plot(resultscrs1, show = "genotypes", type = "stacked")
par(op)
## ----rps4, message=F----------------------------------------------
afcrs2 <- allFitnessEffects(genotFitness = crs(10, 1, 1),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## ----rps4b, eval=FALSE--------------------------------------------
# resultscrs2 <- oncoSimulPop(10,
# afcrs2,
# model = "McFL",
# onlyCancer = FALSE,
# finalTime = 100,
# mu = 1e-2,
# initSize = 4000,
# keepPhylog = TRUE,
# seed = NULL,
# errorHitMaxTries = FALSE,
# errorHitWallTime = FALSE)
## ----rps5, message=F----------------------------------------------
set.seed(1)
resultscrs2a <- oncoSimulIndiv(afcrs2,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100,
mu = 1e-2,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(resultscrs2a, show = "genotypes", type = "line")
## ----rps6, message=F----------------------------------------------
set.seed(3)
resultscrs2b <- oncoSimulIndiv(afcrs2,
model = "McFL",
onlyCancer = FALSE,
finalTime = 60,
mu = 1e-2,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(resultscrs2b, show = "genotypes", type = "line", cex.lab=1.1,
las = 1)
## ----rps7, message=F----------------------------------------------
afcrs3 <- allFitnessEffects(genotFitness = crs(1, 5, 5),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
resultscrs3 <- oncoSimulIndiv(afcrs3,
model = "McFL",
onlyCancer = FALSE,
finalTime = 60,
mu = 1e-2,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(resultscrs3, show = "genotypes", type = "line", cex.lab=1.1,
las = 1)
## ----hkdv, message=F----------------------------------------------
## Stablish Genotype-Fitnees mapping. D = Dove, H = Hawk
## With newer OncoSimulR functionality, using WT to start the simulation
## would no longer be needed.
H_D_fitness <- function(c, v,
gt = c("WT", "H", "D")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1"),
paste0("1 + f_H *", (v-c)/2, "+ f_D *", v),
paste0("1 + f_D *", v/2)))
}
## Fitness Effects specification
HD_competition <-allFitnessEffects(
genotFitness = H_D_fitness(10, 2,
gt = c("WT", "H", "D")),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## Plot fitness landscape of genotype "H, D" evaluation
data.frame("Doves_fitness" = evalGenotype(genotype = "D",
fitnessEffects = HD_competition,
spPopSizes = c(5000, 5000, 5000)),
"Hawks_fitness" = evalGenotype(genotype = "H",
fitnessEffects = HD_competition,
spPopSizes = c(5000, 5000, 5000))
)
## ----hkdv2, message=F---------------------------------------------
## Simulated trajectories
## run only a few for the sake of speed
simulation <- oncoSimulPop(2,
mc.cores = 2,
HD_competition,
model = "McFL", # There is no collapse
onlyCancer = FALSE,
finalTime = 50,
mu = 1e-2, # Quick emergence of D and H
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## Plot first trajectory as an example
plot(simulation[[1]], show = "genotypes", type = "line",
xlim = c(40, 50),
lwdClone = 2, ylab = "Number of individuals",
main = "Hawk and Dove trajectory",
col = c("#a37acc", "#f8776d", "#7daf00"),
font.main=2, font.lab=2,
cex.main=1.4, cex.lab=1.1,
las = 1)
## ----hkdvx45------------------------------------------------------
## Recover the final result from first simulation
result <- tail(simulation[[1]][[1]], 1)
## Get the number of organisms from each species
n_WT <- result[2]
n_D <- result[3]
n_H <- result[4]
total <- n_WT + n_D + n_H
## Dove percentage
data.frame("Doves" = round(n_D/total, 2)*100,
"Hawks" = round(n_H/total, 2)*100 )
## ----glvop1, message=FALSE----------------------------------------
# Definition of the function for creating the corresponding dataframe.
avc <- function (a, v, c) {
data.frame(Genotype = c("WT", "GLY", "VOP", "DEF"),
Fitness = c("1",
paste0("1 + ",a," * (f_GLY + 1)"),
paste0("1 + ",a," * f_GLY + ",v," * (f_VOP + 1) - ",c),
paste0("1 + ",a," * f_GLY + ",v," * f_VOP")
))
}
# Specification of the different effects on fitness.
afavc <- allFitnessEffects(genotFitness = avc(2.5, 2, 1),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## For real, you would probably want to run
## this multiple times with oncoSimulPop
simulation <- oncoSimulIndiv(afavc,
model = "McFL",
onlyCancer = FALSE,
finalTime = 15,
mu = 1e-3,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----glvop2, message=FALSE----------------------------------------
# Representation of the plot of one simulation as an example (the others are
# highly similar).
plot(simulation, show = "genotypes", type = "line",
ylab = "Number of individuals", main = "Fully glycolytic tumours",
font.main=2, font.lab=2, cex.main=1.4, cex.lab=1.1, las = 1)
## ----glvop3, message=FALSE----------------------------------------
# Definition of the function for creating the corresponding dataframe.
avc <- function (a, v, c) {
data.frame(Genotype = c("WT", "GLY", "VOP", "DEF"),
Fitness = c("1",
paste0("1 + ",a," * (f_GLY + 1)"),
paste0("1 + ",a," * f_GLY + ",v, " * (f_VOP + 1) - ",c),
paste0("1 + ",a," * f_GLY + ",v, " * f_VOP")
))
}
# Specification of the different effects on fitness.
afavc <- allFitnessEffects(genotFitness = avc(2.5, 7, 1),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
simulation <- oncoSimulIndiv(afavc,
model = "McFL",
onlyCancer = FALSE,
finalTime = 15,
mu = 1e-4,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----glvop4, message=FALSE----------------------------------------
## We get a huge number of VOP very quickly
## (too quickly?)
plot(simulation, show = "genotypes", type = "line",
ylab = "Number of individuals", main = "Fully angiogenic tumours",
font.main=2, font.lab=2, cex.main=1.4, cex.lab=1.1, las = 1)
## ----glvop5, message=FALSE----------------------------------------
# Definition of the function for creating the corresponding dataframe.
avc <- function (a, v, c) {
data.frame(Genotype = c("WT", "GLY", "VOP", "DEF"),
Fitness = c("1",
paste0("1 + ",a," * (f_GLY + 1)"),
paste0("1 + ",a," * f_GLY + ",v," * (f_VOP + 1) - ",c),
paste0("1 + ",a," * f_GLY + ",v," * f_VOP")
))
}
# Specification of the different effects on fitness.
afavc <- allFitnessEffects(genotFitness = avc(7.5, 2, 1),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
# Launching of the simulation (20 times).
simulation <- oncoSimulIndiv(afavc,
model = "McFL",
onlyCancer = FALSE,
finalTime = 25,
mu = 1e-4,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----glvop6, message=FALSE----------------------------------------
# Representation of the plot of one simulation as an example (the others are
# highly similar).
plot(simulation, show = "genotypes", type = "line",
ylab = "Number of individuals", main = "Heterogeneous tumours",
font.main=2, font.lab=2, cex.main=1.4, cex.lab=1.1, las = 1)
## ----example5_fitness, message=FALSE------------------------------
fitness_rel <- function(a, b, r, g, gt = c("WT", "S", "I", "D")) {
data.frame(
Genotype = gt,
Fitness = c("1",
paste0("1 + ", a, " * f_D"),
paste0("1 + 1 - ", g),
paste0("1 + (1 - f_I - f_D) * (1 - ", b, " + ",
a, ") + f_I * (1 - ", b, " + ", r,
") + f_D * (1 - 2 * ", b, ") + 1 - ", b,
" + ", a, " + f_I * (", r, " - ",
a, ") - f_D * (", b, " + ", a, ")"))
)
}
## ----example5scen1, message=FALSE---------------------------------
scen1 <- allFitnessEffects(genotFitness = fitness_rel(a = 0.5, b = 0.7,
r = 0.1, g = 0.8),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(1)
simulScen1 <- oncoSimulIndiv(scen1,
model = "McFL",
onlyCancer = FALSE,
finalTime = 70,
mu = 1e-4,
initSize = 5000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
op <- par(mfrow = c(1, 2))
plot(simulScen1, show = "genotypes", type = "line",
main = "First scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
plot(simulScen1, show = "genotypes",
main = "First scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
par(op)
## ----example5scen2, message=FALSE---------------------------------
scen2 <- allFitnessEffects(genotFitness = fitness_rel(a = 0.3, b = 0.7,
r = 0.1, g = 0.7),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(1)
simulScen2 <- oncoSimulIndiv(scen2,
model = "McFL",
onlyCancer = FALSE,
finalTime = 70,
mu = 1e-4,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
op <- par(mfrow = c(1, 2))
plot(simulScen2, show = "genotypes", type = "line",
main = "Second scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
plot(simulScen2, show = "genotypes",
main = "Second scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
par(op)
## ----example5scen3, message=FALSE---------------------------------
scen3 <- allFitnessEffects(genotFitness = fitness_rel(a = 0.2, b = 0.3,
r = 0.1, g = 0.3),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(1)
simulScen3 <- oncoSimulIndiv(scen3,
model = "McFL",
onlyCancer = FALSE,
finalTime = 50,
mu = 1e-4,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
op <- par(mfrow = c(1, 2))
plot(simulScen3, show = "genotypes", type = "line",
main = "Third scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
plot(simulScen3, show = "genotypes",
main = "Third scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
par(op)
## ----example5scen4, message=FALSE---------------------------------
scen4 <- allFitnessEffects(genotFitness = fitness_rel(a = 0.2, b = 0.4,
r = 0.1, g = 0.3),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## Set a different seed to show the results better since
## with set.seed(1) the progression of I cells was not shown
set.seed(2)
simulScen4 <- oncoSimulIndiv(scen4,
model = "McFL",
onlyCancer = FALSE,
finalTime = 40,
mu = 1e-4,
initSize = 4000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
op <- par(mfrow = c(1, 2))
plot(simulScen4, show = "genotypes", type = "line",
main = "Fourth scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
plot(simulScen4, show = "genotypes",
main = "Fourth scenario",
cex.main = 1.4, cex.lab = 1.1,
las = 1)
par(op)
## ----smyeloma, eval=TRUE,echo=FALSE, fig.cap="Multiplication factor in myeloma interaction. Table 1 in Sartakhti et al., 2016, 'Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma' https://doi.org/10.1371/journal.pone.0168856 ."----
knitr::include_graphics("Myeloma_interaction.png")
## ----smyelo56j----------------------------------------------------
f_cells <- function(c1, c2, c3, r11, r12, r13,
r21, r22, r23, r31, r32, r33, M, awt = 1e-4,
gt = c("WT", "OC", "OB", "MM")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("max(0.1, 1 - ", awt, " * (f_OC + f_OB+f_MM)*N)"),
paste0("1", "+(((f_OC * (", M, "-1)+1)*", c1, ")/", M, ")*",r11,
"+((((1-f_MM) * (", M, "-1)-f_OC*(", M, "-1)-1)*", c2, ")/", M, ")*", r12,
"+(((", M, "-(1-f_MM)*(", M, "-1))*", c3, ")/", M, ")*", r13,
"-", c1
),
paste0("1", "+(((f_OB*(", M, "-1)+1)*", c2, ")/", M, ")*", r22,
"+((((1-f_OC)*(", M, "-1)-f_OB*(", M, "-1)-1)*", c3, ")/", M, ")*", r23,
"+(((", M, "-(1-f_OC)*(", M, "-1))*", c1, ")/", M, ")*", r21,
"-", c2
),
paste0("1", "+(((f_MM*(", M, "-1)+1)*", c3, ")/", M, ")*", r33,
"+((((1-f_OB)*(", M, "-1)-f_MM*(", M, "-1)-1)*", c1, ")/", M, ")*", r31,
"+(((", M, "-(1-f_OB)*(", M, "-1))*", c2, ")/", M, ")*", r32,
"-", c3
)
)
,stringsAsFactors = FALSE
)
}
## ----smyelo3v57---------------------------------------------------
N <- 40000
M <- 10
c1 <- 1
c2 <- 1.2
c3 <- 1.4
r11 <- 0
r12 <- 1
r13 <- 2.5
r21 <- 1
r22 <- 0
r23 <- -0.3
r31 <- 2.5
r32 <- 0
r33 <- 0
fe_cells <-
allFitnessEffects(
genotFitness =
f_cells(c1, c2, c3, r11, r12, r13,
r21, r22, r23, r31, r32, r33, M,
gt = c("WT", "OC", "OB", "MM")),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## Simulated trajectories
set.seed(2)
simulation <- oncoSimulIndiv(fe_cells,
model = "McFL",
onlyCancer = FALSE,
finalTime = 20, ## 30
mu = c("OC"=1e-1, "OB"=1e-1, "MM"=1e-4),
initSize = N,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## Plot trajectories
## op <- par(mfrow = c(1, 2))
## plot(simulation, show = "genotypes", type = "line")
plot(simulation, show = "genotypes", thinData = TRUE)
## par(op)
## ----smyeloc1v23--------------------------------------------------
N <- 40000
M <- 10
c1 <- 1
c2 <- 1
c3 <- 1
r11 <- 0
r12 <- 1
r13 <- 0.5
r21 <- 1
r22 <- 0
r23 <- -0.3
r31 <- 0.5
r32 <- 0
r33 <- 0
fe_cells <-
allFitnessEffects(
genotFitness =
f_cells(c1, c2, c3, r11, r12, r13,
r21, r22, r23, r31, r32, r33, M,
gt = c("WT", "OC", "OB", "MM")),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## Simulated trajectories
set.seed(1)
simulation <- oncoSimulIndiv(fe_cells,
model = "McFL",
onlyCancer = FALSE,
finalTime = 15, ## 25
mu = c("OC"=1e-1, "OB"=1e-1, "MM"=1e-4),
initSize = N,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
#Plot trajectorie
plot(simulation, show = "genotypes", thinData = TRUE)
## ----parka , message=FALSE----------------------------------------
park1<- data.frame(Genotype = c("WT", "A", "B", "A,B"),
Fitness = c("1",
"1 + 3*(f_1 + f_2 + f_1_2)",
"1 + 2*(f_1 + f_2 + f_1_2)", ## We establish
## the fitness of B smaller than the one of A because
## it is an indirect cause of the disease and not a direct one.
"1.5 + 4.5*(f_1 + f_2 + f_1_2)")) ## The baseline
## of the fitness is higher in the
## AB population (their growth is favored).
parkgen1<- allFitnessEffects(genotFitness = park1,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## ----parkb--------------------------------------------------------
set.seed(1)
fpark1 <- oncoSimulIndiv(parkgen1,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100,
mu = 1e-4,
initSize = 5000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## ----parkplot1, message=FALSE-------------------------------------
plot(fpark1, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue"))
## ----parkplot2, message=FALSE-------------------------------------
plotClonePhylog(fpark1, N = 0, keepEvents=TRUE, timeEvents=TRUE)
## ----wuAMicrobesfit1----------------------------------------------
create_fe <- function(bG, cG, iPA, cI, cS, bPA, ab,
gt = c("WT", "CT", "PA")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ", bG, " * (f_ + f_CT) - ", cS,
" * (f_ + f_CT + f_PA) - ", cI, "(f_PA > 0.2) - ", cG,
" - ", ab),
paste0("1 + ", bG, " * (f_ + f_CT) - ", cS,
" * (f_ + f_CT + f_PA) - ", cG),
paste0("1 +", bPA, " - ", cS, " * (f_ + f_CT + f_PA) - ", iPA,
" *(f_(f_PA > 0.2))")),
stringsAsFactors = FALSE)
}
## ----wuAMicrobescheck---------------------------------------------
create_fe("bG", "cG", "iPA", "cI", "cS", "bPA", "ab")
## ----wuAMicrobes2a------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(7, 1, 9, 0.5, 2, 5, 0),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(1000, 1000, 1000))
## ----wuAMicrobes2b------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(7, 1, 9, 0.5, 2, 5, 2),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(1000, 1000, 1000))
## ----wuAMicrobes2c------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(7, 1, 9, 0.5, 2, 5, 2),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(0, 0, 1000))
## ----wuAMicrobes2d------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(7, 1, 9, 0.5, 2, 5, 2),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(100, 0, 1000))
## ----wuAMicrobes2e------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(7, 1, 9, 0.5, 2, 5, 5),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(1000, 0, 0))
## ----wuAMicrobes2f------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(7, 1, 9, 0.5, 2, 5, 5),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(1000, 0, 1000))
## ----woAntib1, eval = FALSE---------------------------------------
# woAntib <- allFitnessEffects(
# genotFitness = create_fe(7, 1, 9, 0.5, 2, 5, 0),
# frequencyDependentFitness = TRUE,
# frequencyType = "rel")
#
# ## We do not run this for speed but load it below
# set.seed(2)
# woAntibS <- oncoSimulIndiv(woAntib,
# model = "McFL",
# onlyCancer = FALSE,
# finalTime = 2000,
# mu = 1e-4,
# initSize = 1000,
# keepPhylog = FALSE,
# seed = NULL,
# errorHitMaxTries = FALSE,
# errorHitWallTime = FALSE,
# keepEvery = 2 ## store a smaller object
# )
#
## ----woAntib1data-------------------------------------------------
## Load stored results
data(woAntibS)
## ----woAntib2-----------------------------------------------------
plot(woAntibS, show = "genotypes", type = "line",
col = c("black", "green", "red"))
## ----wiAntib1-----------------------------------------------------
wiAntib <- allFitnessEffects(
genotFitness = create_fe(7, 1, 9, 0.5, 2, 5, 2),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(2)
wiAntibS <- oncoSimulIndiv(wiAntib,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100,
mu = 1e-4,
initSize = 1000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(wiAntibS, show = "genotypes", type = "line",
col = c("black", "green", "red"))
## ----breastCfit1--------------------------------------------------
create_fe <- function(cG, bG, cS, cMMph, cMMTC, bR, cD,
gt = c("WT", "Mph", "BTC", "MTC")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ", bG, "*(f_ + f_Mph) - ", cG, " - ", cS, "*(f_ + f_BTC)"),
paste0("1 + ", bG, "*(f_ + f_Mph) - ", cG, " - ", cMMph),
paste0("1 + ", bR, " + ", bG, "*(f_ + f_Mph) - ", cS, "* (f_ + f_BTC) -",
cD , " * f_Mph"),
paste0("1 + ", bR, " + ", bG, " *(f_ + f_Mph) -", cMMTC, " - ",
cD , " * f_Mph")
),
stringsAsFactors = FALSE)
}
## ----breastCcheck-------------------------------------------------
create_fe("cG", "bG","cS", "cMMph", "cMMTC", "bR", "cD")
## ----breastC2a----------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(2, 5, 1, 0.8, 1, 1, 9),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(WT = 1000, Mph = 0, BTC = 0, MTC = 0))
## ----breastC2b----------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(2, 5, 1, 0.8, 1, 1, 9),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(WT = 1000, Mph = 1000, BTC = 0, MTC = 0))
## ----breastC2c----------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(2, 5, 1, 0.8, 1, 1, 9),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(WT = 1000, Mph = 1000, BTC = 100, MTC = 100))
## ----cancercontrol1-----------------------------------------------
afe_3_a <- allFitnessEffects(
genotFitness =
create_fe(0.5, 4, 1, 0.2, 1, 0.5, 4),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(2)
s_3_a <- oncoSimulIndiv(afe_3_a,
model = "McFL",
onlyCancer = FALSE,
finalTime = 50,
mu = 1e-4,
initSize = 10000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s_3_a, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue", "yellow"))
## ----cancerNM1----------------------------------------------------
afe_3_a <- allFitnessEffects(
genotFitness =
create_fe(1, 4, 0.5, 1, 1.5, 1, 4),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(2)
s_3_a <- oncoSimulIndiv(afe_3_a,
model = "McFL",
onlyCancer = FALSE,
finalTime = 50,
mu = 1e-4,
initSize = 10000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s_3_a, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue", "yellow"))
## ----cancerM1-----------------------------------------------------
afe_3_a <- allFitnessEffects(
genotFitness =
create_fe(0.5, 4, 2, 0.5, 0.5, 1, 4),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(2)
s_3_a <- oncoSimulIndiv(afe_3_a,
model = "McFL",
onlyCancer = FALSE,
finalTime = 50,
mu = 1e-4,
initSize = 10000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s_3_a, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue", "yellow"))
## ----breastCQfit1-------------------------------------------------
create_fe <- function(cG, bG, cS, cMMph, cMMTC, bR, cD, Q,
gt = c("WT", "BTC", "R", "MTC", "Mph", "BTC,R", "MTC,R")) {
data.frame(Genotype = gt,
Fitness = c(
paste0("1 + ", bG, "(f_ + f_R + f_Mph) - ", cG, " - ", cS, "(f_ + f_BTC + f_R + f_BTC_R) -",
"0.01*", Q),
paste0("1 + ", bR, " + ", bG, "(f_ + f_R + f_Mph) - ", cS, " (f_ + f_BTC + f_R + f_BTC_R) -",
cD , " * f_Mph -", Q),
paste0("1 + ", bG, "(f_ + f_R + f_Mph) - ", cG, " - ", cS, "(f_ + f_BTC + f_R + f_BTC_R)"),
paste0("1 + ", bR, " + ", bG, " *(f_ + f_R + f_Mph) -", cMMTC, " - ",
cD , " * f_Mph -", Q),
paste0("1 + ", bG, "(f_ + f_R + f_Mph) - ", cG, " - ", cMMph, "- 0.01*",Q),
paste0("1 + ", bR, " + ", bG, "(f_ + f_R + f_Mph) - ", cS, " (f_ + f_BTC + f_R + f_BTC_R) -",
cD , " * f_Mph"),
paste0("1 + ", bR, " + ", bG, " *(f_ + f_R + f_Mph) -", cMMTC, " - ",
cD , " * f_Mph")
),
stringsAsFactors = FALSE)
}
## ----breastCQcheck------------------------------------------------
create_fe("cG", "bG","cS", "cMMph", "cMMTC", "bR", "cD", "Q")
## ----breastCQ2a---------------------------------------------------
evalAllGenotypes(allFitnessEffects(genotFitness =
create_fe(2,5,1,0.8,1,1,9,5),
frequencyDependentFitness = TRUE,
frequencyType = "rel"),
spPopSizes = c(WT = 1000, BTC = 100, R = 0,
MTC = 100, Mph = 1000,
"BTC, R" = 0, "MTC, R" = 0))
## ----cancerwoQ1---------------------------------------------------
afe_3_a <- allFitnessEffects(
genotFitness =
create_fe(2, 5, 1, 0.8, 1, 1, 9, 0),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
#Set mutation rates
muvar2 <- c("Mph" = 1e-2, "BTC" = 1e-3, "MTC"=1e-3, "R" = 1e-7)
set.seed(2)
s_3_a <- oncoSimulIndiv(afe_3_a,
model = "McFL",
onlyCancer = FALSE,
finalTime = 20,
mu = muvar2,
initSize = 10000,
keepPhylog = TRUE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s_3_a, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue", "pink", "orange", "brown"))
## ----cancerwQlRm1-------------------------------------------------
afe_3_a <- allFitnessEffects(
genotFitness =
create_fe(2, 5, 1, 0.8, 1, 1, 9, 2),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
muvar2 <- c("Mph" = 1e-2, "BTC" = 1e-3, "MTC"=1e-3, "R" = 1e-7)
set.seed(2)
s_3_a <- oncoSimulIndiv(afe_3_a,
model = "McFL",
onlyCancer = FALSE,
finalTime = 20,
mu = muvar2,
initSize = 10000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s_3_a, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue", "pink", "orange", "brown"))
## ----cancerwQHRm1-------------------------------------------------
afe_3_a <- allFitnessEffects(
genotFitness =
create_fe(2, 5, 1, 0.8, 1, 1, 9, 2),
frequencyDependentFitness = TRUE,
frequencyType = "rel")
muvar2 <- c("Mph" = 1e-2, "BTC" = 1e-3, "MTC"=1e-3, "R" = 1e-5)
set.seed(2)
s_3_a <- oncoSimulIndiv(afe_3_a,
model = "McFL",
onlyCancer = FALSE,
finalTime = 20, ## short for speed; increase for "real"
mu = muvar2,
initSize = 10000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
plot(s_3_a, show = "genotypes", type = "line",
col = c("black", "green", "red", "blue", "pink", "orange", "brown"))
## ----timefdf1-----------------------------------------------------
## Fitness definition
fl <- data.frame(
Genotype = c("WT", "A", "B"),
Fitness = c("1", #WT
"if (T>50) 1.5; else 0;", #A
"0*f_") , #B
stringsAsFactors = FALSE
)
fe <- allFitnessEffects(genotFitness = fl,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## Evaluate the fitness before and after the specified currentTime
evalAllGenotypes(fe, spPopSizes = c(100, 100, 100))
evalAllGenotypes(fe, spPopSizes = c(100, 100, 100), currentTime = 80)
## Simulation
sim <- oncoSimulIndiv(fe,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100,
mu = 0.01,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL,
errorHitMaxTries = FALSE,
errorHitWallTime = FALSE)
## Plot the results
plot(sim, show = "genotypes")
## ----adapChemo1---------------------------------------------------
a <- 1; b <- 0.5; c <- 0.5 ## a b c
d <- 1; e <- 1.25; f <- 0.7 ## d e f
g <- 0.975; h <- -0.5; i <- 0.75 ## g h i
payoff_m <- matrix(c(a,b,c,d,e,f,g,h,i), ncol=3, byrow=TRUE)
colnames(payoff_m) <- c("Healthy", "Chemo-sensitive", "Chemo-resistant")
rownames(payoff_m) <- c("Healthy", "Chemo-sensitive", "Chemo-resistant")
print(payoff_m <- as.table(payoff_m))
## ----adapChemo2---------------------------------------------------
print( df <- data.frame(
CellType = c("H", "S", "R"),
Fitness = c("F(H) = ax(H) + bx(S) + cx(R)", #Healthy
"F(S) = dx(H) + ex(S) + fx(R)", #Sensitive
"F(R) = gx(H) + hx(S) + ix(R)")), #Resistant
row.names = FALSE )
## ----scenChemo1---------------------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## Coefficients
# Healthy Sensitive Resistant
a=3; b=1.5; c=1.5 # Healthy
d=4; e=5; f=2.8 # Sensitive
g=3.9; h=-2; i=2.2 # Resistant
# Here we divide coefficients to reduce the amount of cells obtained in the simulation.
# We have divided a, b and c by 3, and d, e and i by 4.
# Healthy Sensitive Resistant
a <- 1; b <- 0.5; c <- 0.5 # Healthy
d <- 1; e <- 1.25; f <- 0.7 # Sensitive
g <- 0.975; h <- -0.5; i <- 0.75 # Resistant
## Fitness definition
players <- data.frame(Genotype = c("WT","S","R","S,R"),
Fitness = c(paste0(a, "*f_+", b, "*f_S+", c, "*f_S_R"), #WT
paste0(d,"*f_+",e,"*f_S+",f,"*f_S_R"), #S
"0", #R
paste0(g,"*f_+",h,"*f_S+",i,"*f_S_R")), #S,R
stringsAsFactors = FALSE)
game <- allFitnessEffects(genotFitness = players,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## Plot the first scenario
eag <- evalAllGenotypes(game, spPopSizes = c(10,1,0,10))[c(1, 3, 4),]
plot(eag)
## Simulation
gamesimul <- oncoSimulIndiv(game,
model = "McFL",
onlyCancer = FALSE,
finalTime = 40,
mu = 0.01,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL)
## Plot 2
plot(gamesimul, show = "genotypes", type = "line",
col = c("black", "green", "red"), ylim = c(20, 50000))
plot(gamesimul, show = "genotypes")
## ----fixedChemo1--------------------------------------------------
# Effect of drug on fitness sensible tumor cells
drug_eff <- 0.01
wt_fitness <- paste0(a, "*f_+", b, "*f_S+", c, "*f_S_R")
sens_fitness <- paste0(d, "*f_+", e, "*f_S+", f, "*f_S_R")
res_fitness <- paste0(g, "*f_+", h, "*f_S+", i, "*f_S_R")
players_1 <- data.frame(Genotype = c("WT", "S", "R", "S, R"),
Fitness = c(wt_fitness, #WT
paste0("if (T>50) ", drug_eff, "*(",sens_fitness, ")",";
else ", sens_fitness, ";"), #S
"0", #R
res_fitness), #S,R
stringsAsFactors = FALSE)
period_1 <- allFitnessEffects(genotFitness = players_1,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(2)
final_time <- 170 ## for speed
simul_period_1 <- oncoSimulIndiv(period_1,
model = "McFL",
onlyCancer = FALSE,
finalTime = final_time,
mu = 0.01,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL)
# ylim has been adapted to number of cells
plot(simul_period_1, show = "genotypes", type = "line",
col = c("black", "green", "red"), ylim = c(20, 300000),
thinData = TRUE)
## plot(simul_period_1, show = "genotypes", ylim = c(20, 12000))
## ----switchChemo1-------------------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
# Healthy Sensitive Resistant
a <- 1; b <- 0.5; c <- 0.5 # Healthy
d <- 1; e <- 1.25; f <- 0.7 # Sensitive
g <- 0.975; h <- -0.5; i <- 0.75 # Resistant
wt_fitness <- paste0(a, "*f_+", b, "*f_S+", c, "*f_S_R")
sens_fitness <- paste0(d, "*f_+", e, "*f_S+", f, "*f_S_R")
res_fitness <- paste0(g, "*f_+", h, "*f_S+", i, "*f_S_R")
fitness_df <-data.frame(Genotype = c("WT", "S", "R", "S, R"),
Fitness = c(wt_fitness, #WT
paste0("if (T>50) (sin(T+2)/10) * (", sens_fitness,")",
"; else ", sens_fitness, ";"), #S
"0", #R
res_fitness), #S,R
stringsAsFactors = FALSE)
afe <- allFitnessEffects(genotFitness = fitness_df,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
switching_sim <- oncoSimulIndiv(afe,
model = "McFL",
onlyCancer = FALSE,
finalTime = 100,
mu = 0.01,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL)
plot(switching_sim, show = "genotypes", type = "line",
col = c("black", "green", "red"), ylim = c(20, 200000))
## plot(switching_sim, show = "genotypes", ylim = c(20, 1000))
## ----gfChemo1-----------------------------------------------------
# WT Cooperators Defectors Overproducers
a <- 1; b <- 0.5; c <- 0.5; m <- 0.75 ## a b c m
d <- 1; e <- 1.25; f <- 0.7; o <- 0.185 ## d e f o
g <- 1; h <- 1.5; i <- 0.5; p <- 2.5 ## g h i p
j <- 0.8; k <- 1; l <- 0.5; q <- 1.5 ## j k l q
payoff_m <- matrix(c(a,b,c,m,d,e,f,o,g,h,i,p,j,k,l,q), ncol=4, byrow=TRUE)
colnames(payoff_m) <- c("WT", "Cooperators", "Defectors", "Overproducers")
rownames(payoff_m) <- c("WT", "Cooperators", "Defectors", "Overproducers")
print(payoff_m <- as.table(payoff_m))
## ----gfChemo2-----------------------------------------------------
print( df <- data.frame(
CellType = c("WT", "C", "D", "P"),
Fitness = c("F(WT) = ax(WT) + bx(C) + cx(D) + mx(P)",
"F(C) = dx(WT) + ex(C) + fx(D) + ox(P)",
"F(D) = gx(WT) + hx(C) + ix(D) + px(P)",
"F(P) = jx(WT) + kc(C) + lx(D) + qx(P)")),
row.names = FALSE )
## ----scenGF1------------------------------------------------------
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
## Coefficients
## New coefficients for the interaction with overproducing sensitive:
# WT COOPERATOR DEFECTOR OVERPRODUCER
a <- 1; b <- 0.5; c <- 0.5; m <- 0.75 # WT
wt_fitness <- paste0(a, "*f_+", b, "*f_C+", c, "*f_C_D+", m, "*f_C_P")
d <- 1; e <- 1.25; f <- 0.7; o <- 1.875 # Cooperator
coop_fitness <- paste0(d, "*f_+", e, "*f_C+", f, "*f_C_D+", o, "*f_C_P")
g <- 1; h <- 1.5; i <- 0.5; p <- 2.5 # Defector
def_fitness <- paste0(g, "*f_+", h, "*f_C+", i, "*f_C_D+", p, "*f_C_P")
j <- 0.8; k <- 1; l <- 0.5; q <- 1.5 # Cooperator overproducing
over_fitness <- paste0(j, "*f_+", k, "*f_C+", l, "*f_C_D+", q, "*f_C_P")
## No-chemotherapy
## Fitness definition
coop_no <- data.frame(Genotype = c("WT", "C", "D", "P", "C,D", "C,P", "D,P", "C,D,P"),
Fitness = c(
wt_fitness, #WT
coop_fitness, #S
"0", #D
"0", #P
def_fitness, #S,D
over_fitness, #S,P
"0", #D,P
"0" #C,D,P
),
stringsAsFactors = FALSE)
game_no <- allFitnessEffects(genotFitness = coop_no,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
## First plot
eag <- evalAllGenotypes(game_no,
spPopSizes = c(WT = 10, C = 10, D = 0, P = 0,
"C, D" = 10, "C, P" = 1,
"D, P" = 0, "C, D, P" = 0))[c(1, 2, 5, 6),]
plot(eag)
## Simulation
gamesimul_no <- oncoSimulIndiv(game_no,
model = "McFL",
onlyCancer = FALSE,
finalTime = 35,
mu = 0.01,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL)
## Second plot
plot(gamesimul_no, show = "genotypes", type = "line",
col = c("blue", "red", "green", "purple"), ylim = c(20, 50000),
thinData = TRUE)
# Third plot
## plot(gamesimul_no, show = "genotypes")
## ----scenGFChemo1-------------------------------------------------
## Chemotherapy - GF Impairing
# Effect of drug on GF availability
# This term is multiplied by the fitness, and reduces the GF available
drug_eff <- 0.25
coop_fix <- data.frame(Genotype = c("WT", "C", "D", "P", "C,D", "C,P", "D,P", "C,D,P"),
Fitness = c(
wt_fitness, #WT
paste0("if (T>50) ", drug_eff, "* 1.2 *(", coop_fitness, ")",
"; else ", coop_fitness, ";"), #C
"0", #D
"0", #P
paste0("if (T>50) ", drug_eff, "*(", def_fitness, ")",
"; else ", def_fitness, ";"), #C,D
paste0("if (T>50) ", drug_eff, "* 1.5 * (", over_fitness, ")",
"; else ", over_fitness, ";"), #C,P **
"0", #D,P
"0" #C,D,P
),
stringsAsFactors = FALSE)
## ** The drug effect is 1.5 times the original because of the overproduction of GF and the
## full availability of this molecule inside the producing subclone.
period_fix <- allFitnessEffects(genotFitness = coop_fix,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(2)
final_time <- 30 ## you'd want this longer; short for speed of vignette
simul_period_fix <- oncoSimulIndiv(period_fix,
model = "McFL",
onlyCancer = FALSE,
finalTime = final_time,
mu = 0.01,
initSize = 5000,
keepPhylog = FALSE,
seed = NULL)
# First plot
plot(simul_period_fix, show = "genotypes", type = "line",
col = c("blue", "red", "green", "purple"), ylim = c(20, 50000),
thinData = TRUE)
# Second plot
## plot(simul_period_fix, show = "genotypes", ylim = c(20, 8000))
## ----exTimeInc----------------------------------------------------
dfT1 <- data.frame(Genotype = c("WT", "A", "B"),
Fitness = c("1",
"if (T>50) 1 + 2.35*f_; else 0.50;",
"if (T>200) 1 + 0.45*(f_ + f_1); else 0.50;"),
stringsAsFactors = FALSE)
afeT1 <- allFitnessEffects(genotFitness = dfT1,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(1)
simT1 <- oncoSimulIndiv(afeT1,
model = "Exp",
mu = 1e-5,
initSize = 1000,
finalTime = 500,
onlyCancer = FALSE,
seed = NULL)
plot(simT1, show = "genotypes", type = "line")
## ----exTimeInc1---------------------------------------------------
evalAllGenotypes(afeT1, spPopSizes = c(10,10,10), currentTime = 49)[c(2,3), ]
evalAllGenotypes(afeT1, spPopSizes = c(10,10,10), currentTime = 51)[c(2,3), ]
evalAllGenotypes(afeT1, spPopSizes = c(10,10,10), currentTime = 201)[c(2,3), ]
## ----exTimeDec----------------------------------------------------
dfT2 <- data.frame(Genotype = c("WT", "A", "B"),
Fitness = c(
"1",
"if (T>0 and T<50) 0; else if (T>100 and T<150) 0.05; else 1.2 + 0.35*f_;",
"0.8 + 0.45*(f_)"
),
stringsAsFactors = FALSE)
afeT2 <- allFitnessEffects(genotFitness = dfT2,
frequencyDependentFitness = TRUE,
frequencyType = "rel")
set.seed(1)
simT2 <- oncoSimulIndiv(afeT2,
model = "McFL",
mu = 1e-5,
initSize = 10000,
finalTime = 225,
onlyCancer = FALSE,
seed = NULL)
plot(simT2, show = "genotypes", thinData = TRUE)
## ----examplesTDec1------------------------------------------------
evalAllGenotypes(afeT2, spPopSizes = c(100,10,10), currentTime = 49)[c(2,3), ]
evalAllGenotypes(afeT2, spPopSizes = c(100,10,10), currentTime = 51)[c(2,3), ]
evalAllGenotypes(afeT2, spPopSizes = c(100,10,10), currentTime = 101)[c(2,3), ]
evalAllGenotypes(afeT2, spPopSizes = c(100,10,10), currentTime = 201)[c(2,3), ]
## ----examplesTCol-------------------------------------------------
dfT3 <- data.frame(Genotype = c("WT", "A", "B"),
Fitness = c(
"1",
"1 + 0.2 * (n_2 > 10)",
"if (T>50 and T<80) 0.80; else 0.9 + 0.4 * (n_1 > 10)"),
stringsAsFactors = FALSE)
afeT3 <- allFitnessEffects(genotFitness = dfT3,
frequencyDependentFitness = TRUE,
frequencyType = "abs")
set.seed(2)
simT3 <- oncoSimulIndiv(afeT3,
model = "McFLD",
mu = 1e-4,
initSize = 5000,
finalTime = 500,
onlyCancer = FALSE,
seed = NULL,
errorHitWallTime = FALSE,
errorHitMaxTries = FALSE)
plot(simT3, show = "genotypes", type = "line")
## ----examplesTCol1------------------------------------------------
evalAllGenotypes(afeT3, spPopSizes = c(10,10,10), currentTime = 30)[c(2,3), ]
evalAllGenotypes(afeT3, spPopSizes = c(11,11,11), currentTime = 79)[c(2,3), ]
evalAllGenotypes(afeT3, spPopSizes = c(11,11,11), currentTime = 81)[c(2,3), ]
## ----lod_pom_ex---------------------------------------------------
pancr <- allFitnessEffects(
data.frame(parent = c("Root", rep("KRAS", 4), "SMAD4", "CDNK2A",
"TP53", "TP53", "MLL3"),
child = c("KRAS","SMAD4", "CDNK2A",
"TP53", "MLL3",
rep("PXDN", 3), rep("TGFBR2", 2)),
s = 0.05, sh = -0.3, typeDep = "MN"))
pancr16 <- oncoSimulPop(16, pancr, model = "Exp",
mc.cores = 2)
## Look a the first POM
str(POM(pancr16)[1:3])
LOD(pancr16)[1:2]
## The diversity of LOD (lod_single) and POM might or might not
## be identical
diversityPOM(POM(pancr16))
diversityLOD(LOD(pancr16))
## Show the genotypes and their diversity (which might, or might
## not, differ from the diversity of LOD and POM)
sampledGenotypes(samplePop(pancr16))
## -----------------------------------------------------------------
## No seed fixed, so reruns will give different DAGs.
(a1 <- simOGraph(10))
library(graph) ## for simple plotting
plot(as(a1, "graphNEL"))
## ----simographindirect, eval=FALSE,echo=TRUE----------------------
# g2 <- simOGraph(4, out = "rT", removeDirectIndirect = FALSE)
#
# fe_from_d <- allFitnessEffects(g2)
# fitness_d <- evalAllGenotypes(fe_from_d)
#
# fe_from_t <- allFitnessEffects(genotFitness =
# OncoSimulR:::allGenotypes_to_matrix(fitness_d))
#
# ## Compare
# fitness_d
# (fitness_t <- evalAllGenotypes(fe_from_t))
#
# identical(fitness_d, fitness_t)
#
#
# ## ... but to be safe use fe_from_t as the fitnessEffects object for simulations
#
## -----------------------------------------------------------------
## This code will only be evaluated under Windows
if(.Platform$OS.type == "windows")
try(pancrError <- oncoSimulPop(10, pancr,
initSize = 1e-5,
detectionSize = 1e7,
keepEvery = 10,
mc.cores = 2))
## -----------------------------------------------------------------
## Do not run under Windows
if(.Platform$OS.type != "windows")
pancrError <- oncoSimulPop(10, pancr,
initSize = 1e-5,
detectionSize = 1e7,
keepEvery = 10,
mc.cores = 2)
## ---- eval=FALSE--------------------------------------------------
# pancrError[[1]]
## ---- eval=FALSE--------------------------------------------------
# pancrError[[1]][1]
## ----ex-tomlin1exc------------------------------------------------
sd <- 0.1 ## fitness effect of drivers
sm <- 0 ## fitness effect of mutator
nd <- 20 ## number of drivers
nm <- 5 ## number of mutators
mut <- 50 ## mutator effect THIS IS THE DIFFERENCE
fitnessGenesVector <- c(rep(sd, nd), rep(sm, nm))
names(fitnessGenesVector) <- 1:(nd + nm)
mutatorGenesVector <- rep(mut, nm)
names(mutatorGenesVector) <- (nd + 1):(nd + nm)
ft <- allFitnessEffects(noIntGenes = fitnessGenesVector,
drvNames = 1:nd)
mt <- allMutatorEffects(noIntGenes = mutatorGenesVector)
## ----ex-tomlinexc2------------------------------------------------
ddr <- 4
set.seed(2)
RNGkind("L'Ecuyer-CMRG")
st <- oncoSimulPop(4, ft, muEF = mt,
detectionDrivers = ddr,
finalTime = NA,
detectionSize = NA,
detectionProb = NA,
onlyCancer = TRUE,
keepEvery = NA,
mc.cores = 2, ## adapt to your hardware
seed = NULL) ## for reproducibility
## set.seed(NULL) ## return things to their "usual state"
## -----------------------------------------------------------------
sessionInfo()
## ----last, echo=FALSE---------------------------------------------
paste(difftime(Sys.time(), time0, units = "mins"), "minutes")
## ----timeit-------------------------------------------------------
## The 15 most time consuming chunks
sort(unlist(all_times), decreasing = TRUE)[1:15]
## ----sumtimeit----------------------------------------------------
paste("Sum times of chunks = ", sum(unlist(all_times))/60, " minutes")
## ---- echo=FALSE, eval=TRUE---------------------------------------
## reinitialize the seed
set.seed(NULL)