Simulating epistatic genotype-phenotype maps

Simulate rough, epistatic genotype-phenotype maps using the simulate module.

LinearSimulation

The following examples show a variety ways to simulate a genotype-phenotype map with linear, high-order epistatic interactions. The simulation interface provides methods to easily dictate the construction of a simulated genotype-phenotype map.

from epistasis.simulate import LinearSimulation

# Define the wildtype sequence and possible mutations at each site.
wildtype = "0000"
mutations = {
    0: ["0", "1"], # mutation alphabet for site 0
    1: ["0", "1"],
    2: ["0", "1"],
    3: ["0", "1"]
}
# Initialize a simulation
gpm = LinearSimulation(wildtype, mutations)

# Set the order of epistasis
gpm.set_coefs_order(4)

# Generate random epistatic coefficients
coef_range = (-1, 1) # coefs between -1 and 1
gpm.set_coefs_random(coef_range)

Alternatively, you can quickly simulate a binary genotype-phenotype map if you’re fine with a simple, binary alphabet at each site.

# define the length of genotypes and the order of epistasis
length = 4
gpm = LinearSimulation.from_length(length)

# Generate random epistatic coefs
gpm.set_coefs_order(4)
gpm.set_coefs_random(coef_range)

For all simulated genotype-phenotype maps, one can initialize a genotype-phenotype map from an existing dataset. Scroll through class methods that start with from_ to see all options for initializing simulated genotype-phenotype maps.

NonlinearSimulation

Simulate a nonlinear, epistatic genotype-phenotype map using NonlinearSimulation. Simply define a function which transforms a linear genotype-phenotype map onto a nonlinear scale. Note, the function must have x as the first argument. This argument represents the linearized phenotypes to be transformed.

from epistasis.simulate import NonlinearSimulation

def saturating_scale(x, K):
    return ((K+1)*x)/(K+x)

# Define the initial value for the paramter, K
p0 = [2]

gpm = NonlinearSimulation.from_length(4, function=saturating_scale, p0=p0)
gpm.set_coefs_order(4)
gpm.set_coefs_random((0,1))

Multiplicative Example

Multiplicative epistasis is a common nonlinear, phenotypic scale. Simulate this type of map using the NonlinearSimulation class.

\[\begin{split}\begin{eqnarray} p & = & \beta_1 \beta_2 \beta_{1,2} \\ p & = & e^{ln(\beta_1) + ln(\beta_2) + ln(\beta_{1,2})} \end{eqnarray}\end{split}\]

Using the epistasis package, this looks like the following example. First, define the exponential function as the nonlinear scale passed into the Simulation class.

import numpy as np
from epistasis.simulation import NonlinearSimulation

def multiplicative(x):
    return np.exp(x)

gpm = NonlinearSimulation.from_length(4, function=multiplicative)

Then, define the epistatic coefficients, take their log, and pass them into the simulation object.

# Set the order of epistasis
gpm.set_coefs_order(4)

# generate random coefs
coefs = np.random.uniform(0,3, size=len(gpm.epistasis.labels))

# Take the log of the coefs
log_coefs = np.log(coefs)

# Pass coefs into the simulation class.
gpm.set_coefs_values(log_coefs)