# Spread of a pathogen in a homogeneous population In nosoi: A Forward Agent-Based Transmission Chain Simulator

knitr::opts_chunk$set( collapse = TRUE, comment = "#>" )  nosoi can accommodate a wide range of epidemiological transmission scenarios. It hence relies on many parameters, that need to be set properly for the right scenario to be simulated. This tutorial aims to illustrate how to set up a nosoi simulation for a "simple" case: a pathogen being transmitted within a population without structure. We will present two cases, first for a single-host, and then a dual-host pathogen. # Setting up the simulation The wrapper function nosoiSim takes all the arguments that will be passed down to the simulator, in the case of this tutorial singleNone (for "single host, no structure"). We thus start by providing the options type="single" and popStructure="none" to set up the analysis: SimulationSingle <- nosoiSim(type="single", popStructure="none", ...)  This simulation type requires several arguments or options in order to run, namely: • length.sim • max.infected • init.individuals • pExit with param.pExit and timeDep.pExit • nContact with param.nContact and timeDep.nContact • pTrans with param.pTrans and timeDep.pTrans • prefix.host • progress.bar • print.step All the param.* elements provide individual-level parameters to be taken into account, while the timeDep.* elements inform the simulator if the "absolute" simulation time should be taken into account. ## General parameters length.sim, max.infected and init.individuals are general parameters that define the simulation: • length.sim is the maximum number of time units (e.g. days, months, years, or another time unit of choice) during which the simulation will be run. • max.infected is the maximum number of individuals that can be infected during the simulation. • init.individuals defines the number of individuals (an integer above 1) that will start a transmission chain (there will be as many transmission chains as initial individuals that "seed" the epidemic process). Here, we will run a simulation starting with 1 individual, for a maximum of 1,000 infected individuals and a maximum time of 300 days. SimulationSingle <- nosoiSim(type="single", popStructure="none", length.sim=300, max.infected=1000, init.individuals=1, ...)  ## Core functions The core functions pExit, nContact and pTrans each follow the same principles to be set up. To accommodate for different scenarios, they can be constant, time-dependent (using the relative time since infection t for each individual or the "absolute" time pres.time of the simulation) or even individually parameterized, to include some stochasticity at the individual-host level. In any case, the provided function, like all other core functions in nosoi, has to be expressed as a function of time t, even if time is not used to compute the probability. In case the function uses individual-based parameters, they must be specified in a list of functions (called param.pExit, param.nContact or param.pTrans) (see Get started). If no individual-based parameters are used, then these lists are set to NA. Keep in mind that pExit and pTrans have to return a probability (i.e. a number between 0 and 1) while nContact should return a natural number (positive integer or zero). Several parameters, such as the time since infection, the "absolute" time of the simulation and individual-based parameters can be combined within the same function. In any case, time since infection and "absolute" time should ALWAYS be designated by t and prestime respectively. They also have to be used in the order: (1) t; (2) prestime and (3) individual-based parameters. This is necessary for the function to be properly parsed by nosoi. ### pExit, param.pExit and timeDep.pExit • pExit is the first required fundamental parameter and provides a daily probability for a host to leave the simulation (either cured, died, etc.). • param.pExit is the list of functions needed to individually parameterize pExit (see Get started). The name of each function in the list has to match the name of the parameter it is sampling for pExit. • timeDep.pExit allows for pExit to be dependent on the "absolute" time of the simulation, to account - for example - for seasonality or other external time-related covariates. By default, timeDep.pExit is set to FALSE. ### nContact, param.nContact and timeDep.nContact • nContact represents the number (expressed as a positive integer) of potentially infectious contacts an infected hosts can encounter per unit of time. At each time point, a number of contacts will be determined for each active host in the simulation. The number of contacts (i.e. the output of your function) has to be an integer and can be set to zero. • param.nContact is the list of functions needed to individually parameterize nContact (see Get started). The name of each function in the list has to match the name of the parameter it is sampling for nContact. • timeDep.nContact allows for nContact to be dependent on the "absolute" time of the simulation, to account - for example - for seasonality or other external time-related covariates. By default, timeDep.nContact is set to FALSE. ### pTrans, param.pTrans and timeDep.pTrans • pTrans is the heart of the transmission process and represents the probability of transmission over time (when a contact occurs). • param.pTrans is the list of functions needed to individually parameterize pTrans (see Get started). The name of each function in the list has to match the name of the parameter it is sampling for pTrans. • timeDep.pTrans allows for pTrans to be dependent on the "absolute" time of the simulation, to account - for example - for seasonality or other external time-related covariates. By default, timeDep.pTrans is set to FALSE. ## Miscellaneous prefix.host allows you to define the first character(s) for the hosts' unique ID. It will be followed by a hyphen and a unique number. By default, prefix.host is "H" for "Host". print.progress allows you to have some information printed on the screen about the simulation as it is running. It will print something every print.step. By default, print.progress is activated with a print.step = 10 (you can change this frequency), but you may want to deactivate it by setting print.progress=FALSE. ## Dual host In the case of a dual host simulation, several parameters of the nosoiSim will have to be specified for each host type, designated by A and B. The wrapper function nosoiSim will then take all the arguments that will be passed down to the simulator, in the case of this tutorial dualNone (for "dual host, no structure"). We thus start by providing the options type="dual" and popStructure="none" to set up the analysis: SimulationDual <- nosoiSim(type="dual", popStructure="none", ...)  As with singleNone, this function takes several arguments or options to be able to run, namely: • length.sim • max.infected.A • max.infected.B • init.individuals.A • init.individuals.B • pExit.A with param.pExit.A and timeDep.pExit.A • nContact.A with param.nContact.A and timeDep.nContact.A • pTrans.A with param.pTrans.A and timeDep.pTrans.A • prefix.host.A • pExit.B with param.pExit.B and timeDep.pExit.B • nContact.B with param.nContact.B and timeDep.nContact.B • pTrans.B with param.pTrans.B and timeDep.pTrans.B • prefix.host.B • print.progress • print.step As you can see, host-type dependent parameters are now designated by the suffix .A or .B. Both max.infected.A and max.infected.B have to be provided to set an upper limit on the simulation size. To initiate the simulation, you have to provide at least one starting host, either A or B in init.individuals.A or init.individuals.B respectively. If you want to start the simulation with one host only, then the init.individuals of the other can be set to 0. # Running nosoi ## Single host We present here a very simple simulation for a single host pathogen. ### pExit For pExit, we choose a constant value, namely 0.08, i.e. an infected host has 8% chance to leave the simulation at each unit of time: p_Exit_fct <- function(t){return(0.08)}  Remember that pExit, like the other core functions has to be function of t, even if t is not used. Since pExit is constant here, there is no use for the "absolute" time of the simulation nor for the individual-based parameters. So param.pExit=NA, and timeDep.pExit=FALSE. ### nContact For nContact, we choose a constant function that will draw a value from a normal distribution with mean = 0.5 and sd = 1, round it, and take its absolute value: n_contact_fct = function(t){abs(round(rnorm(1, 0.5, 1), 0))}  The distribution of nContact looks as follows: if (!requireNamespace("ggplot2", quietly = TRUE)) { message("Package 'ggplot2' is needed for plotting this figure.") } else { library(ggplot2) library(dplyr) set.seed(4099) data = data.frame(N=abs(round(rnorm(200, 0.5, 1), 0))) data = data %>% group_by(N) %>% summarise(freq=length(N)/200) ggplot(data=data, aes(x=as.factor(N), y=freq)) + geom_bar(stat="identity") + theme_minimal() + labs(x="nContact",y="Frequency") }  At each time step and for each infected host, nContact will be drawn anew. Remember that nContact, like the other core functions has to be function of t, even if t is not used. Since nContact is constant here, there is no use for the "absolute" time of the simulation nor for the individual-based parameters. So param.nContact=NA, and timeDep.nContact=FALSE. ### pTrans We choose pTrans in the form of a threshold function: before a certain amount of time since initial infection, the host does not transmit (incubation time, which we call t_incub), and after that time it will transmit with a certain (constant) probability (which we call p_max). This function is dependent on the time since the host's infection t: p_Trans_fct <- function(t, p_max, t_incub){ if(t < t_incub){p=0} if(t >= t_incub){p=p_max} return(p) }  Because each host is different (slightly different biotic and abiotic factors), you can expect each host to exhibit differences in the dynamics of infection, and hence the probability of transmission over time. Thus, t_incub and p_max will be sampled for each host individually according to a certain distribution. t_incub will be sampled from a normal distribution of$mean$= 7 and$sd$= 1, while p_max will be sampled from a beta distribution with shape parameters$\alpha$= 5 and$\beta$= 2: t_incub_fct <- function(x){rnorm(x,mean = 7,sd=1)} p_max_fct <- function(x){rbeta(x,shape1 = 5,shape2=2)}  Note that here t_incub and p_max are functions of x and not t (they are not core functions but individual-based parameters), and x enters the function as the number of draws to make. Taken together, the profile for pTrans for a subset of 200 individuals in the population will look as follows: if (!requireNamespace("ggplot2", quietly = TRUE)) { message("Package 'ggplot2' is needed for plotting this figure.") } else { library(ggplot2) library(dplyr) set.seed(99) p_Trans_fct <- function(t, p_max, t_incub){ if(t < t_incub){p=0} if(t >= t_incub){p=p_max} return(p) } t_incub_fct <- function(x){rnorm(x,mean = 7,sd=1)} p_max_fct <- function(x){rbeta(x,shape1 = 5,shape2=2)} data = data.frame(t_incub=t_incub_fct(200),p_max=p_max_fct(200),host=paste0("H-",1:200)) t=c(0:12) data3=NULL for(t in 0:15){ data2 = data %>% group_by(host) %>% mutate(proba=p_Trans_fct(t=t,p_max=p_max, t_incub=t_incub)) data2$t = t
data3 = rbind(data3, data2)
}

ggplot(data=data3, aes(x=t, y=proba,group=host)) + geom_line(color="grey60") + theme_minimal() + labs(x="Time since infection (t)",y="pTrans")
}


pTrans is not dependent on the "absolute" time of the simulation, so timeDep.pTrans=FALSE. However, since we make use of individual-based parameters, we have to provide a param.pTrans as a list of functions. The name of each element within this list should have the same name that the core function (here pTrans) uses as argument, e.g.:

t_incub_fct <- function(x){rnorm(x,mean = 7,sd=1)}
p_max_fct <- function(x){rbeta(x,shape1 = 5,shape2=2)}

param_pTrans = list(p_max=p_max_fct, t_incub=t_incub_fct)


### Running

Once nosoiSim is set up, you can run the simulation (here the "seed" ensures that you will obtain the same results as in this tutorial):

library(nosoi)

#pExit
p_Exit_fct  <- function(t){return(0.08)}

#nContact
n_contact_fct = function(t){abs(round(rnorm(1, 0.5, 1), 0))}

#pTrans
p_Trans_fct <- function(t,p_max,t_incub){
if(t < t_incub){p=0}
if(t >= t_incub){p=p_max}
return(p)
}

t_incub_fct <- function(x){rnorm(x,mean = 7,sd=1)}
p_max_fct <- function(x){rbeta(x,shape1 = 5,shape2=2)}

param_pTrans = list(p_max=p_max_fct,t_incub=t_incub_fct)

# Starting the simulation ------------------------------------

set.seed(805)
SimulationSingle <- nosoiSim(type="single", popStructure="none",
length.sim=100, max.infected=100, init.individuals=1,
nContact=n_contact_fct,
param.nContact=NA,
timeDep.nContact=FALSE,
pExit = p_Exit_fct,
param.pExit=NA,
timeDep.pExit=FALSE,
pTrans = p_Trans_fct,
param.pTrans = param_pTrans,
timeDep.pTrans=FALSE,
prefix.host="H",
print.progress=FALSE)


Once the simulation has finished, it reports the number of time units for which the simulation has run (r SimulationSingle$total.time), and the maximum number of infected hosts (r SimulationSingle$host.info.A$N.infected). Note that the simulation has stopped here before reaching length.sim as it has crossed the max.infected threshold set at 100. ## Dual host Setting up a dual host simulation is similar to the single host version described above, but each parameter has to be provided for both hosts. Here, we choose for Host A the same parameters as the single / only host above. Host B will have sightly different parameters: ### pExit.B For pExit.B, we choose a value that depends on the "absolute" time of the simulation, for example cyclic climatic conditions (temperature). In that case, the function's arguments should be t and prestime (the "absolute" time of the simulation), in that order: p_Exit_fctB <- function(t,prestime){(sin(prestime/(2*pi*10))+1)/16} #for a periodic function  The values of pExit.B across the "absolute time" of the simulation will be the following: p_Exit_fctx <- function(x){(sin(x/(2*pi*10))+1)/16} #for a periodic function if (!requireNamespace("ggplot2", quietly = TRUE)) { message("Package 'ggplot2' is needed for plotting this figure.") } else { ggplot(data=data.frame(x=0), aes(x=x)) + stat_function(fun=p_Exit_fctx) + theme_minimal() + labs(x="Absolute time (prestime)",y="pExit") + xlim(0,360) }  Since pExit.B is dependent on the simulation's absolute time, do not forget to set timeDep.pExit.B to TRUE. Since there are no individual-based parameters, param.pExit.B=NA. ### nContact.B For nContact.B, we choose a constant function that will sample a value out of a provided range of possible values, each with a certain probability: n_contact_fct.B = function(t){sample(c(0,1,2),1,prob=c(0.6,0.3,0.1))}  The distribution of nContact.B looks as follows: if (!requireNamespace("ggplot2", quietly = TRUE)) { message("Package 'ggplot2' is needed for plotting this figure.") } else { library(ggplot2) library(dplyr) set.seed(9898) data = data.frame(N=sample(c(0,1,2),200,replace=TRUE,prob=c(0.6,0.3,0.1))) data = data %>% group_by(N) %>% summarise(freq=length(N)/200) ggplot(data=data, aes(x=as.factor(N), y=freq)) + geom_bar(stat="identity") + theme_minimal() + labs(x="nContact.B",y="Frequency") }  At each time and for each infected host, nContact.B will be drawn anew. Remember that nContact.B, like the other core functions has to be function of t, even if t is not used. Since nContact.B is constant here, there is no use for the "absolute" time of the simulation nor for the individual-based parameters. So param.nContact.B=NA, and timeDep.nContact.B=FALSE. ### pTrans.B We choose pTrans.B in the form of a Gaussian function. It will reach its maximum value at a certain time point (mean) after initial infection and will subsequently decrease until it reaches 0: p_Trans_fct.B <- function(t, max.time){ dnorm(t, mean=max.time, sd=2)*5 }  Because each host is different (slightly different biotic and abiotic factors), you can expect each host to exhibit differences in the dynamics of infection, and hence the probability of transmission over time. Thus, max.time will be sampled for each host individually according to a certain distribution. max.time will be sampled from a normal distribution of parameters$mean$= 5 and$sd$= 1: max.time_fct <- function(x){rnorm(x,mean = 5,sd=1)}  Note again that here max.time is a function of x and not t (not a core function but individual-based parameters), and x enters the function as the number of draws to make. Taken together, the profile for pTrans for a subset of 200 individuals in the population will look as follows: if (!requireNamespace("ggplot2", quietly = TRUE)) { message("Package 'ggplot2' is needed for plotting this figure.") } else { library(ggplot2) library(dplyr) set.seed(7979) p_Trans_fct <- function(t, max.time){ dnorm(t, mean=max.time, sd=2)*5 } max.time_fct <- function(x){rnorm(x,mean = 5,sd=1)} data = data.frame(max.time=max.time_fct(200),host=paste0("H-",1:200)) t=c(0:12) data3=NULL for(t in 0:15){ data2 = data %>% group_by(host) %>% mutate(proba=p_Trans_fct(t=t,max.time=max.time)) data2$t = t
data3 = rbind(data3, data2)
}

ggplot(data=data3, aes(x=t, y=proba,group=host)) + geom_line(color="grey60",alpha=0.3) + theme_minimal() + labs(x="Time since infection (t)",y="pTrans")
}


Since pTrans.B is not dependent on the "absolute" time of the simulation, timeDep.pTrans.B=FALSE. However, since we make use of individual-based parameters, we have to provide a param.pTrans as a list of functions. The name of each element of the list should have the same name as the core function (here pTrans.B) uses as argument, as shown here:

max.time_fct <- function(x){rnorm(x,mean = 5,sd=1)}

param_pTrans.B = list(max.time=max.time_fct)


### Running

Once nosoiSim is set up, you can run the simulation (here the "seed" ensures that you will obtain the same results as in this tutorial):

library(nosoi)

#HostA ------------------------------------

#pExit
p_Exit_fct.A  <- function(t){return(0.08)}

#nContact
n_contact_fct.A = function(t){abs(round(rnorm(1, 0.5, 1), 0))}

#pTrans
p_Trans_fct.A <- function(t,p_max,t_incub){
if(t < t_incub){p=0}
if(t >= t_incub){p=p_max}
return(p)
}

t_incub_fct <- function(x){rnorm(x,mean = 7,sd=1)}
p_max_fct <- function(x){rbeta(x,shape1 = 5,shape2=2)}

param_pTrans.A = list(p_max=p_max_fct,t_incub=t_incub_fct)

#Host B ------------------------------------

#pExit
p_Exit_fct.B  <- function(t,prestime){(sin(prestime/(2*pi*10))+1)/16}

#nContact
n_contact_fct.B = function(t){sample(c(0,1,2),1,prob=c(0.6,0.3,0.1))}

#pTrans
p_Trans_fct.B <- function(t, max.time){
dnorm(t, mean=max.time, sd=2)*5
}

max.time_fct <- function(x){rnorm(x,mean = 5,sd=1)}

param_pTrans.B = list(max.time=max.time_fct)

# Starting the simulation ------------------------------------

set.seed(606)
SimulationDual <- nosoiSim(type="dual", popStructure="none",
length.sim=100,
max.infected.A=100,
max.infected.B=100,

init.individuals.A=1,
init.individuals.B=0,

nContact.A=n_contact_fct.A,
param.nContact.A=NA,
timeDep.nContact.A=FALSE,
pExit.A=p_Exit_fct.A,
param.pExit.A=NA,
timeDep.pExit.A=FALSE,
pTrans.A=p_Trans_fct.A,
param.pTrans.A=param_pTrans.A,
timeDep.pTrans.A=FALSE,
prefix.host.A="H",

nContact.B=n_contact_fct.B,
param.nContact.B=NA,
timeDep.nContact.B=FALSE,
pExit.B=p_Exit_fct.B,
param.pExit.B=NA,
timeDep.pExit.B=TRUE,
pTrans.B=p_Trans_fct.B,
param.pTrans.B=param_pTrans.B,
timeDep.pTrans.B=FALSE,
prefix.host.B="V",

print.progress=FALSE)


Once the simulation has finished, it reports the number of time units for which the simulation has run (r SimulationDual$total.time), and the maximum number of infected hosts A (r SimulationDual$host.info.A$N.infected) and hosts B (r SimulationDual$host.info.B\$N.infected). Note that the simulation has stopped here before reaching length.sim as it has crossed the max.infected.A threshold set at 100.

# Going further

To analyze and visualize your nosoi simulation output, you can have a look on this page.

You may also want to compose a more complex model by adding some structure (e.g. geography) to your simulation. Two tutorials can guide you on how to set up such structured scenarios:

A practical example using a dual host type of simulation without population structure is also available:

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nosoi documentation built on Aug. 17, 2021, 5:09 p.m.