SITH.R
In SITH: A Spatial Model of Intra-Tumor Heterogeneity

## ---- include = FALSE---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>"
)
options(width = 800)
options(rmarkdown.html_vignette.check_title = FALSE)

## ----setup, echo = -3---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
set.seed(1126490984)
library(SITH)
rgl::setupKnitr()

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out <- simulateTumor(max_pop = 250000, verbose = FALSE)

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names(out)
head(out$cell_ids)
head(out$muts)

## ---- echo = FALSE, results = "hide"------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
visualizeTumor(out, background = "white")

## ---- rgl = TRUE, fig.width = 7, fig.height = 5, echo = -2--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
visualizeTumor(out, background = "white")
rgl::view3d(zoom = 0.66)

## ---- rgl = TRUE, fig.width = 7, fig.height = 5, echo = -2--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
visualizeTumor(out, background = "white", plot.type = "heat")
rgl::view3d(zoom = 0.66)

## ---- fig.width = 7.5, fig.height = 4-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
par(mfrow = c(1,2))
plotSlice(tumor = out)
plotSlice(tumor = out, plot.type = "heat")

## ---- fig.width = 7.5, fig.height = 6-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
sp <- spatialDistribution(tumor = out)

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names(sp)

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Scs <- randomSingleCells(tumor = out, ncells = 5, fnr = 0.1)
head(Scs)

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Bulks <- randomBulkSamples(tumor = out, nsamples = 5, cube.length = 7, coverage=100, threshold = 0.05)
head(Bulks)

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Needs <- randomNeedles(tumor = out, nsamples = 5, threshold = 0.05)
head(Needs)

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library(SITH)
set.seed(278115205)

n <- 5
G <- progressionChain(5) 
G

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G[,3] <- rep(0.02, nrow(G))
out <- simulateTumor(max_pop = 1000, disease_model=G)

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out$muts 

## ---- fig.width = 7.5, fig.height = 6-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
plotSlice(out) 

## ---- fig.width = 7.5, fig.height = 6-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
if (!requireNamespace("igraph", quietly = TRUE)) {
  stop("igraph needed to compile the vignette.",
      call. = FALSE)
}

el <- matrix(as.character(c(0,1,0,2,2,3,3,4,2,5,1,5)), ncol = 2, byrow = TRUE)
iG <- igraph::graph_from_edgelist(el)
plot(iG)

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G <- progressionDAG_from_igraph(iG)
G

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out <- simulateTumor(max_pop=5000,disease_model=G, verbose = FALSE)
out$genotypes 

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# Make a chain: 0 -> 1 -> 2
G <- progressionChain(2)

#Give a disadvantage to a cell in state 1 and an advantage to a cell in state 2 
G[1,4] <- 0.9; G[2,4] <- 1.4
G[,3] <- c(0.005,0.005)
G

#Simulate the model with N = 250000 cells
out <- simulateTumor(disease_model=G)

## ---- fig.width = 7.5, fig.height = 6-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
plotSlice(out)

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out$color_scheme 

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out$muts

out$genotypes

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sessionInfo()