Package 'nempi'

Title: Inferring unobserved perturbations from gene expression data
Description: Takes as input an incomplete perturbation profile and differential gene expression in log odds and infers unobserved perturbations and augments observed ones. The inference is done by iteratively inferring a network from the perturbations and inferring perturbations from the network. The network inference is done by Nested Effects Models.
Authors: Martin Pirkl [aut, cre]
Maintainer: Martin Pirkl <[email protected]>
License: GPL-3
Version: 1.15.0
Built: 2024-11-29 06:42:30 UTC
Source: https://github.com/bioc/nempi

Help Index


Classification

Description

Builds and uses different classifiers to infer perturbation profiles

Usage

classpi(
  D,
  unknown = "",
  full = TRUE,
  method = "svm",
  size = NULL,
  MaxNWts = 10000,
  ...
)

Arguments

D

either a binary effects matrix or log odds matrix as for Nested Effects Models (see package 'nem')

unknown

colname of samples without mutation data, E.g. ""

full

if FALSE, does not change the known profiles

method

either one of svm, nn, rf

size

parameter for neural network (see package 'nnet')

MaxNWts

parameters for neural network (see package 'nnet')

...

additional parameters for mnem::nem

Value

plot

Author(s)

Martin Pirkl

Examples

D <- matrix(rnorm(1000*100), 1000, 100)
colnames(D) <- sample(seq_len(5), 100, replace = TRUE)
Gamma <- matrix(sample(c(0,1), 5*100, replace = TRUE, p = c(0.9, 0.1)), 5,
100)
Gamma <- apply(Gamma, 2, function(x) return(x/sum(x)))
Gamma[is.na(Gamma)] <- 0
rownames(Gamma) <- seq_len(5)
result <- classpi(D)

Main function for NEM based perturbation imputation.

Description

Infers perturbations profiles based on a sparse perturbation matrix and differential gene expression as log odds

Usage

nempi(
  D,
  unknown = "",
  Gamma = NULL,
  type = "null",
  full = TRUE,
  verbose = FALSE,
  logtype = 2,
  null = TRUE,
  soft = TRUE,
  combi = 1,
  converged = 0.1,
  complete = TRUE,
  mw = NULL,
  max_iter = 100,
  keepphi = TRUE,
  start = NULL,
  phi = NULL,
  ...
)

Arguments

D

either a binary effects matrix or log odds matrix as for Nested Effects Models (see package 'nem')

unknown

colname of samples without mutation data, E.g. ""

Gamma

matrix with expectations of perturbations, e.g. if you have a binary mutation matrix, just normalize the columns to have sum 1

type

"null": does not use the unknown samples for inference at the start, "random" uses them in a random fashion (not recommended)

full

if FALSE, does not change the known profiles

verbose

if TRUE gives more output during inference

logtype

log type for the log odds

null

if FALSE does not use a NULL node for uninformative samples

soft

if FALSE discretizes Gamma during the inference

combi

if combi > 1, uses a more complex algorithm to infer combinatorial perturbations (experimental)

converged

the absolute difference of log likelihood till convergence

complete

if TRUE uses the complete-data logliklihood (recommended for many E-genes)

mw

if NULL infers mixture weights, otherwise keeps them fixed

max_iter

maximum iterations of the EM algorithm

keepphi

if TRUE, uses the previous phi for the next inference, if FALSE always starts with start network (and empty and full)

start

starting network as adjacency matrix

phi

if not NULL uses only this phi and does not infer a new one

...

additional parameters for the nem function (see package mnem, function nem or mnem::nem)

Value

nempi object

Author(s)

Martin Pirkl

Examples

D <- matrix(rnorm(1000*100), 1000, 100)
colnames(D) <- sample(seq_len(5), 100, replace = TRUE)
Gamma <- matrix(sample(c(0,1), 5*100, replace = TRUE, p = c(0.9, 0.1)), 5,
100)
Gamma <- apply(Gamma, 2, function(x) return(x/sum(x)))
Gamma[is.na(Gamma)] <- 0
rownames(Gamma) <- seq_len(5)
result <- nempi(D, Gamma = Gamma)

Bootstrapping function

Description

Bootstrap algorithm to get a more stable result.

Usage

nempibs(D, bsruns = 100, bssize = 0.5, replace = TRUE, ...)

Arguments

D

either a binary effects matrix or log odds matrix as

bsruns

number of bootstraps

bssize

number of E-genes for each boostrap

replace

if TRUE, actual bootstrap, if False sub-sampling

...

additional parameters for the function nempi

Value

list with aggregate Gamma and aggregate causal network phi

Author(s)

Martin Pirkl

Examples

D <- matrix(rnorm(1000*100), 1000, 100)
colnames(D) <- sample(seq_len(5), 100, replace = TRUE)
Gamma <- matrix(sample(c(0,1), 5*100, replace = TRUE, p = c(0.9, 0.1)), 5,
100)
Gamma <- apply(Gamma, 2, function(x) return(x/sum(x)))
Gamma[is.na(Gamma)] <- 0
rownames(Gamma) <- seq_len(5)
result <- nempibs(D, bsruns = 3, Gamma = Gamma)

Accuracy computation

Description

Compares the ground truth of a perturbation profile with the inferred profile

Usage

pifit(x, y, D, unknown = "", balanced = FALSE, propagate = TRUE, knowns = NULL)

Arguments

x

object of class nempi

y

object of class mnemsim

D

data matrix

unknown

label for the unlabelled samples

balanced

if TRUE, computes balanced accuracy

propagate

if TRUE, propagates the perturbation through the network

knowns

subset of P-genes that are known to be perturbed (the other are neglegted)

Value

list of different accuracy measures: true/false positives/negatives, correlation, area under the precision recall curve, (balanced) accuracy

Author(s)

Martin Pirkl

Examples

library(mnem)
seed <- 42
Pgenes <- 10
Egenes <- 10
samples <- 100
uninform <- floor((Pgenes*Egenes)*0.1)
Nems <- mw <- 1
noise <- 1
multi <- c(0.2, 0.1)
set.seed(seed)
simmini <- simData(Sgenes = Pgenes, Egenes = Egenes,
Nems = Nems, mw = mw, nCells = samples,
uninform = uninform, multi = multi,
badCells = floor(samples*0.1))
data <- simmini$data
ones <- which(data == 1)
zeros <- which(data == 0)
data[ones] <- rnorm(length(ones), 1, noise)
data[zeros] <- rnorm(length(zeros), -1, noise)
lost <- sample(1:ncol(data), floor(ncol(data)*0.5))
colnames(data)[lost] <- ""
res <- nempi(data)
fit <- pifit(res, simmini, data)

Plotting nempi

Description

Plot function for an object of class 'nempi'.

Usage

## S3 method for class 'nempi'
plot(x, barlist = list(), heatlist = list(), ...)

Arguments

x

object of class 'nempi'

barlist

additional arguments for function 'barplot' from package 'graphics'

heatlist

additional arguments for function 'HeatmapOP' from package 'epiNEM'

...

additional arguments for function 'plotDnf' from package 'mnem'

Value

Plots of the optimal network phi and perturbation matrix.

Author(s)

Martin Pirkl

Examples

D <- matrix(rnorm(1000*100), 1000, 100)
colnames(D) <- sample(seq_len(5), 100, replace = TRUE)
result <- nempi(D)
plot(result)

Plot convergence of EM

Description

Produces different convergence plots based on a nempi object

Usage

## S3 method for class 'nempi'
plotConvergence(x, type = "b", ...)

Arguments

x

nempi object

type

see ?plot.default

...

additional parameters for plot

Value

plot

Author(s)

Martin Pirkl

Examples

D <- matrix(rnorm(1000*100), 1000, 100)
colnames(D) <- sample(seq_len(5), 100, replace = TRUE)
Gamma <- matrix(sample(c(0,1), 5*100, replace = TRUE, p = c(0.9, 0.1)), 5,
100)
Gamma <- apply(Gamma, 2, function(x) return(x/sum(x)))
Gamma[is.na(Gamma)] <- 0
rownames(Gamma) <- seq_len(5)
result <- nempi(D, Gamma = Gamma)
par(mfrow=c(2,3))
plotConvergence(result)