allFitnessEffects: Create fitness effects specification from restrictions, epistasis, and order effects.

Description

Given one or more of a set of poset restrictions, epistatic interactions, order effects, and genes without interactions, as well as, optionally, a mapping of genes to modules, return the complete fitness specification.

The output of this function is not intended for user consumption, but as a way of preparing data to be sent to the C++ code.

Usage

allFitnessEffects(rT = NULL, epistasis = NULL, orderEffects = NULL, noIntGenes = NULL, geneToModule = NULL, drvNames = NULL, keepInput = TRUE)

Arguments

A restriction table that is an extended version of a poset (see poset ). A restriction table is a data frame where each row shows one edge between a parent and a child. A restriction table contains exactly these columns, in this order:

parent

The identifiers of the parent nodes, in a parent-child relationship. There must be at least on entry with the name "Root".

child

The identifiers of the child nodes.

s

A numeric vector with the fitness effect that applies if the relationship is satisfied.

sh

A numeric vector with the fitness effect that applies if the relationship is not satisfied. This provides a way of explicitly modeling deviatons from the restrictions in the graph, and is discussed in Diaz-Uriarte, 2015.

typeDep

The type of dependency. Three possible types of relationship exist:

AND, monotonic, or CMPN: Like in the CBN model, all parent nodes must be present for a relationship to be satisfied. Specify it as "AND" or "MN" or "monotone".

OR, semimonotonic, or DMPN

A single parent node is enough for a relationship to be satisfied. Specify it as "OR" or "SM" or "semimonotone".

XOR or XMPN

Exactly one parent node must be mutated for a relationship to be satisfied. Specify it as "XOR" or "xmpn" or "XMPN".

In addition, for the nodes that depend only on the root node, you can use "--" or "-" if you want (though using any of the other three would have the same effects if a node that connects to root only connects to root).

epistasis

A named numeric vector. The names identify the relationship, and the numeric value is the fitness effect. For the names, each of the genes or modules involved is separated by a ":". A negative sign denotes the absence of that term.

orderEffects

A named numeric vector, as for epistasis. A ">" separates the names of the genes of modules of a relationship, so that "U > Z" means that the relationship is satisfied when mutation U has happened before mutation Z.

noIntGenes

A numeric vector (optionally named) with the fitness coefficients of genes (only genes, not modules) that show no interactions. These genes cannot be part of modules. But you can specify modules that have no epistatic interactions. See examples and vignette.

Of course, avoid using potentially confusing characters in the names. In particular, "," and ">" are not allowed as gene names.

geneToModule

A named character vector that allows to match genes and modules. The names are the modules, and each of the values is a character vector with the gene names, separated by a comma, that correspond to a module. Note that modules cannot share genes. There is no need for modules to contain more than one gene. If you specify a geneToModule argument, and you used a restriction table, the geneToModule must necessarily contain, in the first position, "Root" (since the restriction table contains a node named "Root"). See examples below.

drvNames

The names of genes that are considered drivers. This is only used for: a) deciding when to stop the simulations, in case you use number of drivers as a simulation stopping criterion (see oncoSimulIndiv); b) for summarization purposes (e.g., how many drivers are mutated); c) in figures. But you need not specifiy anything if you do not want to, and you can pass an empty vector (as character(0)). The default is to assume that all genes that are not in the noIntGenes are drivers.

keepInput

If TRUE, whether to keep the original input. This is only useful for human consumption of the output. It is useful because it is easier to decode, say, the restriction table from the data frame than from the internal representation. But if you want, you can set it to FALSE and the object will be a little bit smaller.

Value

long.rt: The restriction table in "long format", so as to be easy to parse by the C++ code.
long.epistasis: Ditto, but for the epistasis specification.
long.orderEffects: Ditto for the order effects.
long.geneNoInt: Ditto for the non-interaction genes.
geneModule: Similar, for the gene-module correspondence.
graph: An igraph object that shows the restrictions, epistasis and order effects, and is useful for plotting.
drv: The numeric identifiers of the drivers. The numbers correspond to the internal numeric coding of the genes.
rT: If keepInput is TRUE, the original restriction table.
epistasis: If keepInput is TRUE, the original epistasis vector.
orderEffects: If keepInput is TRUE, the original order effects vector.
noIntGenes: If keepInput is TRUE, the original noIntGenes.

Details

This function is used for extremely flexible specification of fitness effects, including posets, XOR relationships, synthetic mortality and synthetic viability, arbitrary forms of epistatis, arbitrary forms of order effects, etc. Please, see the vignette for detailed and commented examples.

References

Diaz-Uriarte, R. (2015). Identifying restrictions in the order of accumulation of mutations during tumor progression: effects of passengers, evolutionary models, and sampling http://www.biomedcentral.com/1471-2105/16/41/abstract

McFarland, C.~D. et al. (2013). Impact of deleterious passenger mutations on cancer progression. Proceedings of the National Academy of Sciences of the United States of America\/, 110(8), 2910--5.

Examples

Run this code

## A simple poset or CBN-like example

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)

plot(cbn1)


## A more complex example, that includes a restriction table
## order effects, epistasis, genes without interactions, and moduels
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 repeatability
noint <- rexp(5, 10)
names(noint) <- paste0("n", 1:5)

fea <- allFitnessEffects(rT = p4, epistasis = epist, orderEffects = oe,
                         noIntGenes = noint, geneToModule = modules)

plot(fea)


## Modules that show, between them,
## no epistasis (so multiplicative effects).
## We specify the individual terms, but no value for the ":".

fnme <- allFitnessEffects(epistasis = c("A" = 0.1,
                                        "B" = 0.2),
                          geneToModule = c("A" = "a1, a2",
                                           "B" = "b1"))

evalAllGenotypes(fnme, order = FALSE, addwt = TRUE)

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