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Gillespie Simulation for Break-Fusion-Bridge (BFB) Processes Modified to support diploid chromosomes (alleles A and B)

bridge_sim.Rd

Simulates the evolution of cells undergoing Break-Fusion-Bridge cycles using a continuous-time Gillespie algorithm. This function models cell birth and death processes with the possibility of BFB events occurring during replication. Cells with amplified hotspots have an increased birth rate. Now supports modeling both alleles (A and B) of each chromosome.

Usage

bridge_sim(
  initial_cells = 1,
  chromosomes = c(1:22, "X", "Y"),
  bin_length = 1e+06,
  birth_rate = 0.1,
  death_rate = 0.001,
  bfb_allele = "1:A",
  normal_dup_rate = 0,
  bfb_prob = 0.5,
  amp_rate = 1,
  del_rate = 1,
  wgd_available = 0,
  wgd_probability = 0.05,
  lambda = 2,
  rate = 20,
  positive_selection_rate = 0,
  negative_selection_rate = 0,
  max_time = 300,
  max_cells = 256,
  first_round_of_bfb = TRUE,
  return_phylo = TRUE,
  breakpoint_support = "uniform",
  hotspot = list(chr = "1:A", pos = 100),
  alpha = NULL,
  beta = NULL,
  custom_breakpoints = NULL
)

Arguments

initial_cells

Numeric. Number of cells at the start of simulation. Default: 1

chromosomes

Character vector. Chromosomes to model (e.g., c("1", "2", "X")). Default: c(1:22, "X", "Y")

bin_length

Numeric. Length of each genomic bin in base pairs. Default: 5e5

birth_rate

Numeric. Base rate at which cells replicate per unit time. Default: 0.1

death_rate

Numeric. Rate at which cells die per unit time. Default: 0.001

bfb_allele

Character. Allele which will be affected by BFB events. Defaul : "1:A"

normal_dup_rate

Numeric. Rate of normal duplication events. Default: 0.5

bfb_prob

Numeric. Probability of BFB event occurring during replication. Default: 0.01

amp_rate

Numeric. Rate of amplification events. Default: 0.1

del_rate

Numeric. Rate of deletion events. Default: 0.1

wgd_available

Numeric. Number of whole-genome duplication events available. Default: 0

wgd_probability

Numeric. Probability of whole-genome duplication event occurring. Default: 0.05

lambda

Rate parameter for Poisson distribution used to sample the number of genomic events per daughter cell

rate

Rate parameter used in amplification/deletion simulations. Length of event is sample from exponential distribution with parameter 1 / rate.

positive_selection_rate

Numeric. Selection advantage for cells with amplified hotspot. Default: 0

negative_selection_rate

Numeric. Selection disadvantage for cells without amplified hotspot. Default: 0

max_time

Numeric. Maximum simulation time. Default: 50

max_cells

Numeric. Maximum number of cells allowed before simulation stops. Default: 100

first_round_of_bfb

Logical. Whether to apply BFB to initial cells. Default: TRUE

return_phylo

Logical. Whether to build and return the phylogenetic tree. Set to FALSE when only CNA data is needed (e.g. ABC or clonal comparison workflows) to skip the expensive tree-building step. Default: TRUE

breakpoint_support

Character. Distribution used for breakpoint selection ("uniform", "beta", etc.). Default: "uniform"

hotspot

Named list. Hotspot positions for each chromosome allele (e.g., list(chr = "1:A", pos = 100), which is default)

alpha

Numeric. First parameter for beta distribution if used for breakpoint selection. Default: NULL

beta

Numeric. Second parameter for beta distribution if used for breakpoint selection. Default: NULL

Value

A list containing:

cells

List of cell chromosome sequences at the end of simulation

cell_history

Data frame with cell birth/death times and lineage information

input_parameters

List of input parameters used in the simulation