Package 'bnem'

Title: Training of logical models from indirect measurements of perturbation experiments
Description: bnem combines the use of indirect measurements of Nested Effects Models (package mnem) with the Boolean networks of CellNOptR. Perturbation experiments of signalling nodes in cells are analysed for their effect on the global gene expression profile. Those profiles give evidence for the Boolean regulation of down-stream nodes in the network, e.g., whether two parents activate their child independently (OR-gate) or jointly (AND-gate).
Authors: Martin Pirkl [aut, cre]
Maintainer: Martin Pirkl <[email protected]>
License: GPL-3
Version: 1.15.0
Built: 2024-10-30 04:28:11 UTC
Source: https://github.com/bioc/bnem

Help Index


Absorption

Description

applies absorption law to a disjuncitve normal form

Usage

absorption(bString, model = NULL)

Arguments

bString

a disjunctive normal form or binary vector according to model

model

Model object including the search space, if available. See CellNOptR::preprocessing.

Value

bString after absorption law

Author(s)

Martin Pirkl

Examples

graph <- c("A+B=C", "A=C")
absorption(graph)

Inverse absorption

Description

applies "inverse" absorption law to a disjuncitve normal form

Usage

absorptionII(bString, model = NULL)

Arguments

bString

a disjunctive normal form or binary vector according to model

model

Model object including the search space, if available. See CellNOptR::preprocessing.

Value

bString after "inverse" absorption law

Author(s)

Martin Pirkl

Examples

graph <- c("A+B=C", "A=C")
absorptionII(graph)

Add noise

Description

Adds noise to simulated data

Usage

addNoise(sim, sd = 1)

Arguments

sim

bnemsim object from simBoolGtn

sd

standard deviation for the rnorm function

Value

noisy fold-change matrix

Author(s)

Martin Pirkl

Examples

sim <- simBoolGtn(Sgenes = 10, maxEdges = 10, negation=0.1,layer=1)
fc <- addNoise(sim,sd=1)

B-Cell receptor signalling perturbations

Description

Processed data from experiments with a stimulated B-Cell receptor (bcr) and perturbed signalling genes. The raw data is available at https://www.ncbi.nlm.nih.gov/geo/ with accession id GSE68761. For the process steps we refer to the publication Martin Pirkl, Elisabeth Hand, Dieter Kube, Rainer Spang, Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models, Bioinformatics, Volume 32, Issue 6, 15 March 2016, Pages 893–900, https://doi.org/10.1093/bioinformatics/btv680. Alternatively see also the function processDataBCR for details and for reproduction.

Usage

bcr

References

Martin Pirkl, Elisabeth Hand, Dieter Kube, Rainer Spang, Analyzing synergistic and non-synergistic interactions in signalling pathways using Boolean Nested Effect Models, Bioinformatics, Volume 32, Issue 6, 15 March 2016, Pages 893–900, https://doi.org/10.1093/bioinformatics/btv680

Examples

data(bcr)

Boolean Nested Effects Model main function

Description

This function takes a prior network and normalized perturbation data as input and trains logical functions on that prior network

Usage

bnem(
  search = "greedy",
  fc = NULL,
  expression = NULL,
  egenes = NULL,
  pkn = NULL,
  design = NULL,
  stimuli = NULL,
  inhibitors = NULL,
  signals = NULL,
  CNOlist = NULL,
  model = NULL,
  sizeFac = 10^-10,
  NAFac = 1,
  parameters = list(cutOffs = c(0, 1, 0), scoring = c(0.1, 0.2, 0.9)),
  parallel = NULL,
  method = "cosine",
  relFit = FALSE,
  verbose = TRUE,
  reduce = TRUE,
  parallel2 = 1,
  initBstring = NULL,
  popSize = 100,
  pMutation = 0.5,
  maxTime = Inf,
  maxGens = Inf,
  stallGenMax = 10,
  relTol = 0.01,
  priorBitString = NULL,
  selPress = c(1.2, 1e-04),
  fit = "linear",
  targetBstring = "none",
  elitism = NULL,
  inversion = NULL,
  selection = c("t"),
  type = "SOCK",
  exhaustive = FALSE,
  delcyc = FALSE,
  seeds = 1,
  maxSteps = Inf,
  node = NULL,
  absorpII = TRUE,
  draw = TRUE,
  prior = NULL,
  maxInputsPerGate = 2
)

Arguments

search

Type of search heuristic. Either "greedy", "genetic" or "exhaustive". "greedy" uses a greedy algorithm to move through the local neighbourhood of a initial hyper-graph. "genetic" uses a genetic algorithm. "exhaustive" searches through the complete search space and is not recommended.

fc

m x l matrix of foldchanges of gene expression values or equivalent input (normalized pvalues, logodds, ...) for m E-genes and l contrasts. If left NULL, the gene expression data is used to calculate naive foldchanges.

expression

Optional normalized m x l matrix of gene expression data for m E-genes and l experiments.

egenes

list object; each list entry is named after an S-gene and contains the names of egenes which are potential children

pkn

Prior knowledge network as output by CellNOptR::readSIF.

design

Optional n x l design matrix with n S-genes and l experiments. If available. If kept NULL, bnem needs either stimuli, inhibitors or a CNOlist object.

stimuli

Character vector of stimuli names.

inhibitors

Character vector of inhibitors.

signals

Optional character vector of signals. Signals are S-genes, which can directly regulate E-genes. If left NULL, all stimuli and inhibitors are defined as signals.

CNOlist

CNOlist object (see package CellNOptR), if available.

model

Model object including the search space, if available. See CellNOptR::preprocessing.

sizeFac

Size factor penelizing the hyper-graph size.

NAFac

factor penelizing NAs in the data.

parameters

parameters for discrete case (not recommended); has to be a list with entries cutOffs and scoring: cutOffs = c(a,b,c) with a (cutoff for real zeros), b (cutoff for real effects), c = -1 for normal scoring, c between 0 and 1 for keeping only relevant between -1 and 0 for keeping only a specific quantile of E-genes, and c > 1 for keeping the top c E-genes; scoring = c(a,b,c) with a (weight for real effects), c (weight for real zeros), b (multiplicator for effects/zeros between a and c);

parallel

Parallelize the search. An integer value specifies the number of threads on the local machine or a list object as in list(c(1,2,3), c("machine1", "machine2", "machine3")) specifies the threads distributed on different machines (local or others).

method

Scoring method can be "cosine", a correlation, or a distance measure. See ?cor and ?dist for details.

relFit

if TRUE a relative fit for each E-gene is computed (not recommended)

verbose

TRUE for verbose output

reduce

if TRUE reduces the search space for exhaustive search

parallel2

if TRUE parallelises the starts and not the search itself

initBstring

Binary vector for the initial hyper-graph.

popSize

Population size (only "genetic").

pMutation

Probability between 0 and 1 for mutation (only "genetic").

maxTime

Define a maximal time (seconds) for the search.

maxGens

Maximal number of generations (only "genetic").

stallGenMax

Maximum number of stall generations (only "genetic").

relTol

Score tolerance for networks defined as optimal but with a lower score as the real optimum (only "genetic").

priorBitString

Binary vector defining hyper-edges which are added to every hyper-graph. E.g. if you know hyper-edge 55 is definitly there and to fix that, set priorBitString[55] <- 1 (only "genetic").

selPress

Selection pressure between 1 and 2 (if fit="linear") and greater 2 (for fit "nonlinear") for the stochastic universal sampling (only "genetic").

fit

"linear" or "nonlinear fit for stochastic universal sampling

targetBstring

define a binary vector representing a network; if this network is found, the computation stops

elitism

Number of best hyper-graphs transferred to the next generation (only "genetic").

inversion

Number of worst hyper-graphs for which their binary strings are inversed (only "genetic").

selection

"t" for tournament selection and "s" for stochastic universal sampling (only "genetic").

type

type of the paralellisation on multpile machines (default: "SOCK")

exhaustive

If TRUE an exhaustive search is conducted if the genetic algorithm would take longer (only "genetic").

delcyc

If TRUE deletes cycles in all hyper-graphs (not recommended).

seeds

how many starts for the greedy search? (default: 1); uses the n-dimensional cube (n = number of S-genes) to maximize search space coverage

maxSteps

Maximal number of steps (only "greedy").

node

vector of S-gene names, which are used in the greedy search; if node = NULL all nodes are considered

absorpII

Use inverse absorption (default: TRUE).

draw

If TRUE draws the network evolution.

prior

Binary vector. A 1 specifies hyper-edges which should not be optimized (only "greedy").

maxInputsPerGate

If no model is supplied, one is created with maxInputsPerGate as maximum number of parents for each hyper-edge.

Value

List object including the optimized hyper-graph, its corresponding binary vector for full hyper-graph and optimized scores.

Author(s)

Martin Pirkl

See Also

nem

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1,
maxInhibit = 2, signals = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
expression <- matrix(rnorm(nrow(slot(CNOlist, "cues"))*10), 10,
nrow(slot(CNOlist, "cues")))
fc <- computeFc(CNOlist, expression)
initBstring <- rep(0, length(model$reacID))
res <- bnem(search = "greedy", model = model, CNOlist = CNOlist,
fc = fc, pkn = PKN, stimuli = "A", inhibitors = c("B","C","D"),
parallel = NULL, initBstring = initBstring, draw = FALSE, verbose = FALSE,
maxSteps = Inf)

Bootstraped Network

Description

Runs Bootstraps on the data

Usage

bnemBs(fc, x = 10, f = 0.5, replace = TRUE, startString = NULL, ...)

Arguments

fc

m x l matrix of foldchanges of gene expression values or equivalent input (normalized pvalues, logodds, ...) for m E-genes and l contrasts. If left NULL, the gene expression data is used to calculate naive foldchanges.

x

number of bootstraps

f

percentage to sample, e.g. f = 0.5 samples only 50 the amount of E-genes as the original data

replace

if TRUE classical bootstrap, if FALSE sub-sampling without replacement

startString

matrix with each row being a string denoting a network to start inference several times with a specific network

...

additional parameters for the bnem function

Value

list with the accumulation of edges in x and the number of bootstraps in n

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1,
maxInhibit = 2, signals = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
expression <- matrix(rnorm(nrow(slot(CNOlist, "cues"))*10), 10,
nrow(slot(CNOlist, "cues")))
fc <- computeFc(CNOlist, expression)
initBstring <- rep(0, length(model$reacID))
res <- bnemBs(search = "greedy", model = model, CNOlist = CNOlist,
fc = fc, pkn = PKN, stimuli = "A", inhibitors = c("B","C","D"),
parallel = NULL, initBstring = initBstring, draw = FALSE, verbose = FALSE,
maxSteps = Inf)

Compute differential effects

Description

computes differential effects given an activation pattern (absolute gene expression or truth table)

Usage

computeFc(CNOlist, y)

Arguments

CNOlist

CNOlist object (see package CellNOptR), if available.

y

activation pattern according to the annotation in CNOlist

Value

numeric matrix with annotated response scheme

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1, maxInhibit = 2,
signals = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
expression <- matrix(rnorm(nrow(slot(CNOlist, "cues"))*10), 10,
nrow(slot(CNOlist, "cues")))
fc <- computeFc(CNOlist, expression)

Convert normal form

Description

converts a disjunctive normal form into a conjunctive normal form and vice versa; input graph as disjunctive normal form like that: c("A+B=D", "C=D", "G+F=U", ...); output is the dual element also in disjunctive normal form;

Usage

convertGraph(g)

Arguments

g

graph in normal form

Value

converted graph normal form

Author(s)

Martin Pirkl

Examples

g <- "A+B=C"
g2 <- convertGraph(g)

Create dummy CNOlist

Description

creates a general CNOlist object from meta information

Usage

dummyCNOlist(
  stimuli = NULL,
  inhibitors = NULL,
  maxStim = 0,
  maxInhibit = 0,
  signals = NULL
)

Arguments

stimuli

Character vector of stimuli names.

inhibitors

Character vector of inhibitors.

maxStim

maximal number of stimulated genes for a single experiment

maxInhibit

maximal number of inhibited genes for a single experiment

signals

Optional character vector of signals. Signals are S-genes, which can directly regulate E-genes. If left NULL, all stimuli and inhibitors are defined as signals.

Value

CNOlist object

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1, maxInhibit = 2,
signals = c("A", "B","C","D"))

Switch between epiNEM and B-NEM

Description

Convert epiNEM model into general Boolean graph. Only needed for comparing accuracy of inferred network for bnem and epiNEM.

Usage

epiNEM2Bg(t)

Arguments

t

full epiNEM model

Value

differential effects pattern

Author(s)

Martin Pirkl

See Also

CreateTopology

Examples

topology <- epiNEM::CreateTopology(3, 1, force = TRUE)
topology <- unlist(unique(topology), recursive = FALSE)
extTopology <- epiNEM::ExtendTopology(topology$model, 100)
b <- epiNEM2Bg(extTopology)

Compute residuals

Description

calculates residuals (data and optimized network do not match) and visualizes them

Usage

findResiduals(
  bString,
  CNOlist,
  model,
  fc = NULL,
  expression = NULL,
  egenes = NULL,
  parameters = list(cutOffs = c(0, 1, 0), scoring = c(0.1, 0.2, 0.9)),
  method = "s",
  sizeFac = 10^-10,
  main = "residuals for decoupled vertices",
  sub = paste0("green residuals are added effects (left positive,",
    " right negative) and red residuals are deleted ", "effects"),
  cut = TRUE,
  parallel = NULL,
  verbose = TRUE,
  ...
)

Arguments

bString

Binary vector denoting the network given a model

CNOlist

CNOlist object (see package CellNOptR), if available.

model

Model object including the search space, if available. See CellNOptR::preprocessing.

fc

m x l matrix of foldchanges of gene expression values or equivalent input (normalized pvalues, logodds, ...) for m E-genes and l contrasts. If left NULL, the gene expression data is used to calculate naive foldchanges.

expression

Optional normalized m x l matrix of gene expression data for m E-genes and l experiments.

egenes

list object; each list entry is named after an S-gene and contains the names of egenes which are potential children

parameters

parameters for discrete case (not recommended); has to be a list with entries cutOffs and scoring: cutOffs = c(a,b,c) with a (cutoff for real zeros), b (cutoff for real effects), c = -1 for normal scoring, c between 0 and 1 for keeping only relevant between -1 and 0 for keeping only a specific quantile of E-genes, and c > 1 for keeping the top c E-genes; scoring = c(a,b,c) with a (weight for real effects), c (weight for real zeros), b (multiplicator for effects/zeros between a and c);

method

Scoring method can be "cosine", a correlation, or a distance measure. See ?cor and ?dist for details.

sizeFac

Size factor penelizing the hyper-graph size.

main

Main title of the figure.

sub

Subtitle of the figure.

cut

If TRUE does not visualize experiments/S-genes which do not have any residuals.

parallel

Parallelize the search. An integer value specifies the number of threads on the local machine or a list object as in list(c(1,2,3), c("machine1", "machine2", "machine3")) specifies the threads distributed on different machines (local or others).

verbose

TRUE for verbose output

...

additional parameters for epiNEM::HeatmapOP

Value

numeric matrices indicating experiments and/or genes, where the network and the data disagree

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1, maxInhibit = 2,
signal = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
expression <- matrix(rnorm(nrow(slot(CNOlist, "cues"))*10), 10,
nrow(slot(CNOlist, "cues")))
fc <- computeFc(CNOlist, expression)
initBstring <- rep(0, length(model$reacID))
res <- bnem(search = "greedy", CNOlist = CNOlist, fc = fc, model = model,
parallel = NULL, initBstring = initBstring, draw = FALSE, verbose = FALSE,
maxSteps = Inf)
rownames(fc) <- seq_len(nrow(fc))
## val <- validateGraph(CNOlist = CNOlist, fc = fc, model = model,
## bString = res$bString, Egenes = 10, Sgene = 4)
residuals <- findResiduals(res$bString, CNOlist, model, fc = fc)

plot bnem opbject

Description

plots the boolen network as disjunctive normal form

Usage

## S3 method for class 'bnem'
plot(x, ...)

Arguments

x

bnemsim object

...

further arguments; see function mnem::plotDnf

Value

plot of boolean network

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1,
maxInhibit = 2, signals = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
expression <- matrix(rnorm(nrow(slot(CNOlist, "cues"))*10), 10,
nrow(slot(CNOlist, "cues")))
fc <- computeFc(CNOlist, expression)
initBstring <- rep(0, length(model$reacID))
res <- bnem(search = "greedy", model = model, CNOlist = CNOlist,
fc = fc, pkn = PKN, stimuli = "A", inhibitors = c("B","C","D"),
parallel = NULL, initBstring = initBstring, draw = FALSE, verbose = FALSE,
maxSteps = Inf, seeds = 10)
plot(res)

Plot Bootstrap result

Description

Shows the result of a Boostrap with either edge frequencies or confidence intervals

Usage

## S3 method for class 'bnemBs'
plot(
  x,
  scale = 3,
  shift = 0.1,
  cut = 0.5,
  dec = 2,
  ci = 0,
  cip = 0.95,
  method = "exact",
  ...
)

Arguments

x

bnemBs object

scale

numeric value for scaling the edgewidth

shift

numeric value for shifting the edgewidth

cut

shows only edges with a fraction larger than cut

dec

integer for function round

ci

if TRUE shows confidence intervals

cip

range for the confidence interval, e.g. 0.95

method

method to use for conidence interval computation (see function binom.confint from package binom)

...

additional parameters for the function mnem::plotDnf

Value

plot of the network from the bootstrap

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1,
maxInhibit = 2, signals = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
expression <- matrix(rnorm(nrow(slot(CNOlist, "cues"))*10), 10,
nrow(slot(CNOlist, "cues")))
fc <- computeFc(CNOlist, expression)
initBstring <- rep(0, length(model$reacID))
res <- bnemBs(search = "greedy", model = model, CNOlist = CNOlist,
fc = fc, pkn = PKN, stimuli = "A", inhibitors = c("B","C","D"),
parallel = NULL, initBstring = initBstring, draw = FALSE, verbose = FALSE,
maxSteps = Inf)

plot simulation object

Description

plots the boolen network from a simulation as disjunctive normal form

Usage

## S3 method for class 'bnemsim'
plot(x, ...)

Arguments

x

bnemsim object

...

further arguments; see function mnem::plotDnf

Value

plot of boolean network

Author(s)

Martin Pirkl

Examples

sim <- simBoolGtn()
plot(sim)

BCR perturbation reproduction

Description

Produce the application data from the BCR paper of Pirkl, et al., 2016, Bioinformatics. Raw data is available at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68761

Usage

processDataBCR(path = "", combsign = FALSE)

Arguments

path

path to the CEL.gz/Cel files

combsign

if TRUE includes all covariates in ComBat analysis to estimate batch effects.

Value

list with the full foldchanges and epxression matrix, a reduced foldchange matrix and the design matrix for the computations

Author(s)

Martin Pirkl

Examples

## Not run: 
processDataBCR()

## End(Not run)
data(bcr)

sample normal form

Description

creates a random normal form or hyper-graph

Usage

randomDnf(
  vertices = 10,
  negation = TRUE,
  max.edge.size = NULL,
  max.edges = NULL,
  dag = FALSE
)

Arguments

vertices

number of vertices

negation

if TRUE, negations (NOT gates) are allowed

max.edge.size

maximal number of inputs per edge

max.edges

maximal number of hyper-edges

dag

if TRUE, graph will be acyclic

Value

random hyper-graph in normal form

Author(s)

Martin Pirkl

Examples

g <- randomDnf(10)

Reduce graph

Description

reduces the size of a graph, if possible, to an equivalent sub-graph

Usage

reduceGraph(bString, model, CNOlist)

Arguments

bString

binary vector indicating the sub-graph given a model

model

Model object including the search space, if available. See CellNOptR::preprocessing.

CNOlist

CNOlist object (see package CellNOptR), if available.

Value

equivalent sub-graph denoted by a bString

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1, maxInhibit = 2,
signal = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
bString <- reduceGraph(rep(1, length(model$reacID)), model, CNOlist)

score a boolean network

Description

computes the score of a boolean network given the model and data

Usage

scoreDnf(
  bString,
  CNOlist,
  fc,
  expression = NULL,
  model,
  method = "cosine",
  sizeFac = 10^-10,
  NAFac = 1,
  parameters = list(cutOffs = c(0, 1, 0), scoring = c(0.25, 0.5, 2)),
  NEMlist = NULL,
  relFit = FALSE,
  verbose = FALSE
)

Arguments

bString

binary string denoting the boolean network

CNOlist

CNOlist object (see package CellNOptR), if available.

fc

m x l matrix of foldchanges of gene expression values or equivalent input (normalized pvalues, logodds, ...) for m E-genes and l contrasts. If left NULL, the gene expression data is used to calculate naive foldchanges.

expression

Optional normalized m x l matrix of gene expression data for m E-genes and l experiments.

model

Model object including the search space, if available. See CellNOptR::preprocessing.

method

Scoring method can be "cosine", a correlation, or a distance measure. See ?cor and ?dist for details.

sizeFac

Size factor penelizing the hyper-graph size.

NAFac

factor penelizing NAs in the data.

parameters

parameters for discrete case (not recommended); has to be a list with entries cutOffs and scoring: cutOffs = c(a,b,c) with a (cutoff for real zeros), b (cutoff for real effects), c = -1 for normal scoring, c between 0 and 1 for keeping only relevant between -1 and 0 for keeping only a specific quantile of E-genes, and c > 1 for keeping the top c E-genes; scoring = c(a,b,c) with a (weight for real effects), c (weight for real zeros), b (multiplicator for effects/zeros between a and c);

NEMlist

NEMlist object (optional)

relFit

if TRUE a relative fit for each E-gene is computed (not recommended)

verbose

TRUE for verbose output

Value

numeric value (score)

Author(s)

Martin Pirkl

Examples

sim <- simBoolGtn()
scoreDnf(sim$bString, sim$CNOlist, sim$fc, model=sim$model)

Sample random network and simulate data

Description

Draws a random prior network, samples a ground truth from the full boolean extension and generates data

Usage

simBoolGtn(
  Sgenes = 10,
  maxEdges = 25,
  stimGenes = 2,
  layer = 1,
  frac = 0.1,
  maxInDeg = 2,
  dag = TRUE,
  maxSize = 2,
  maxStim = 2,
  maxInhibit = 1,
  Egenes = 10,
  flip = 0.33,
  reps = 1,
  keepsif = FALSE,
  negation = 0.25,
  allstim = FALSE,
  and = 0.25,
  positive = TRUE,
  verbose = FALSE
)

Arguments

Sgenes

number of S-genes

maxEdges

number of maximum edges (upper limit) in the DAG

stimGenes

number of stimulated S-genes

layer

scaling factor for the sampling of next Sgene layerof the prior. high (5-10) mean more depth and low (0-2) means more breadth

frac

fraction of hyper-edges in the ground truth (GTN)

maxInDeg

maximum number of incoming hyper-edges

dag

if TRUE, graph will be acyclic

maxSize

maximum number of S-genes in a hyper-edge

maxStim

maximum of stimulated S-genes in an experiment (=data samples)

maxInhibit

maximum number of inhibited S-genes in an experiment (=data samples)

Egenes

number of E-genes per S-gene, e.g. 10 S-genes and 10 E-genes will return 100 E-genes overall

flip

fraction of inhibited E-genes

reps

number of replicates

keepsif

if TRUE does not delete sif file, which encodes the prior network

negation

sample probability for negative or NOT edges

allstim

full network in which all S-genes are also stimulated

and

probability for AND-gates in the GTN

positive

if TRUE, sets all stimulation edges to activation, else samples inhibitory edges by 'negation' probability

verbose

TRUE for verbose output

Value

list with the corresponding prior graph, ground truth network and data

Author(s)

Martin Pirkl

Examples

sim <- simBoolGtn()
plot(sim)

Simulate states

Description

simulates the activation pattern (truth table) of a hyper-graph and annotated perturbation experiments

Usage

simulateStatesRecursive(CNOlist, model, bString, NEMlist = NULL)

Arguments

CNOlist

CNOlist object (see package CellNOptR), if available.

model

Model object including the search space, if available. See CellNOptR::preprocessing.

bString

binary vector denoting the sub-graph given model

NEMlist

NEMlist object only for devel

Value

return the truth tables for certain perturbation experiments as a numeric matrix

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1, maxInhibit = 2,
signal = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
states <- simulateStatesRecursive(CNOlist, model,
rep(1, length(model$reacID)))

transitive closure

Description

calculates transitive closure of a hyper-graph

Usage

transClose(g, max.iter = NULL, verbose = FALSE)

Arguments

g

hyper-graph in normal form

max.iter

maximal iteration till convergence

verbose

TRUE for verbose output

Value

transitive closure in normal form

Author(s)

Martin Pirkl

Examples

g <- c("A=B", "B=C")
gclose <- transClose(g)

transitive reduction

Description

calculates transitive reduction of a hyper-graph in normal form

Usage

transRed(g, max.iter = NULL, verbose = FALSE)

Arguments

g

hyper-graph in normal form

max.iter

maximal number of iterations till convergence

verbose

TRUE for verbose output

Value

transitive reduction of the hyper-graph in normal form

Author(s)

Martin Pirkl

Examples

g <- c("A=B", "A=C", "B=C", "B=D", "!A=D")
gred <- transRed(g)

validate graph

Description

plotting the observed differential effects of an effect reporter and the expected differential effects of the regulating signalling gene

Usage

validateGraph(
  CNOlist,
  fc = NULL,
  expression = NULL,
  model,
  bString,
  Egenes = 25,
  Sgene = 1,
  parameters = list(cutOffs = c(0, 1, 0), scoring = c(0.1, 0.2, 0.9)),
  plot = TRUE,
  disc = 0,
  affyIds = TRUE,
  relFit = FALSE,
  xrot = 25,
  Rowv = FALSE,
  Colv = FALSE,
  dendrogram = "none",
  soft = TRUE,
  colSideColors = NULL,
  affychip = "hgu133plus2",
  method = "s",
  ranks = FALSE,
  breaks = NULL,
  col = "RdYlGn",
  sizeFac = 10^-10,
  order = "rank",
  verbose = TRUE,
  ...
)

Arguments

CNOlist

CNOlist object (see package CellNOptR), if available.

fc

m x l matrix of foldchanges of gene expression values or equivalent input (normalized pvalues, logodds, ...) for m E-genes and l contrasts. If left NULL, the gene expression data is used to calculate naive foldchanges.

expression

Optional normalized m x l matrix of gene expression data for m E-genes and l experiments.

model

Model object including the search space, if available. See CellNOptR::preprocessing.

bString

Binary string denoting the hyper-graph.

Egenes

Maximal number of visualized E-genes.

Sgene

Integer denoting the S-gene. See colnames(getSignals(CNOlist)[[1]]) to match integer with S-gene name.

parameters

parameters for discrete case (not recommended); has to be a list with entries cutOffs and scoring: cutOffs = c(a,b,c) with a (cutoff for real zeros), b (cutoff for real effects), c = -1 for normal scoring, c between 0 and 1 for keeping only relevant between -1 and 0 for keeping only a specific quantile of E-genes, and c > 1 for keeping the top c E-genes; scoring = c(a,b,c) with a (weight for real effects), c (weight for real zeros), b (multiplicator for effects/zeros between a and c);

plot

Plot the heatmap. If FALSE, only corresponding information is printed.

disc

Discretize the data.

affyIds

Experimental. Turn Affymetrix Ids into HGNC gene symbols.

relFit

if TRUE a relative fit for each E-gene is computed (not recommended)

xrot

See function epiNEM::HeatmapOP

Rowv

See function epiNEM::HeatmapOP

Colv

See function epiNEM::HeatmapOP

dendrogram

See function epiNEM::HeatmapOP

soft

if TRUE, assigns weights to the expected pattern

colSideColors

See function epiNEM::HeatmapOP

affychip

Define Affymetrix chip used to generate the data (optional and experimental).

method

Scoring method can be "cosine", a correlation, or a distance measure. See ?cor and ?dist for details.

ranks

if TRUE, turns data into ranks

breaks

See function epiNEM::HeatmapOP

col

See function epiNEM::HeatmapOP

sizeFac

Size factor penelizing the hyper-graph size.

order

Order by "rank", "name" or "none"

verbose

TRUE for verbose output

...

additional arguments for epiNEM::HeatmapOP

Value

lattice object with matrix information

Author(s)

Martin Pirkl

Examples

sifMatrix <- rbind(c("A", 1, "B"), c("A", 1, "C"), c("B", 1, "D"),
c("C", 1, "D"))
temp.file <- tempfile(pattern="interaction",fileext=".sif")
write.table(sifMatrix, file = temp.file, sep = "\t",
row.names = FALSE, col.names = FALSE,
quote = FALSE)
PKN <- CellNOptR::readSIF(temp.file)
CNOlist <- dummyCNOlist("A", c("B","C","D"), maxStim = 1, maxInhibit = 2,
signal = c("A", "B","C","D"))
model <- CellNOptR::preprocessing(CNOlist, PKN, maxInputsPerGate = 100)
expression <- matrix(rnorm(nrow(slot(CNOlist, "cues"))*10), 10,
nrow(slot(CNOlist, "cues")))
fc <- computeFc(CNOlist, expression)
initBstring <- rep(0, length(model$reacID))
res <- bnem(search = "greedy", CNOlist = CNOlist, fc = fc,
model = model, parallel = NULL, initBstring = initBstring, draw = FALSE,
verbose = FALSE, maxSteps = Inf)
rownames(fc) <- seq_len(nrow(fc))
val <- validateGraph(CNOlist = CNOlist, fc = fc, model = model,
bString = res$bString, Egenes = 10, Sgene = 4)