Package 'scTHI'

Title: Indentification of significantly activated ligand-receptor interactions across clusters of cells from single-cell RNA sequencing data
Description: scTHI is an R package to identify active pairs of ligand-receptors from single cells in order to study,among others, tumor-host interactions. scTHI contains a set of signatures to classify cells from the tumor microenvironment.
Authors: Francesca Pia Caruso [aut], Michele Ceccarelli [aut, cre]
Maintainer: Michele Ceccarelli <[email protected]>
License: GPL-2
Version: 1.17.0
Built: 2024-06-30 03:56:59 UTC
Source: https://github.com/bioc/scTHI

Help Index


single cell Tumor Hist Interaction (scTHI)

Description

Indentification of significantly activated ligand-receptor interactions across clusters of cells from single-cell RNA sequencing data. Single-cell RNA sequencing is the reference technique to characterize the heterogeneity of tumor microenvironment. The composition of the various cell types making up the microenvironment can significantly affect the way in which the immune system activates cancer rejection mechanisms. Understanding the cross-talk signals between immune cells and cancer cells is a fundamental for the identification immuno-oncology therapeutic targets. scTHI is a novel method, single cell Tumor-Host Interaction tool (scTHI), to identify significantly activated ligand-receptor interactions across clusters of cells from single-cell RNA sequencing data. cTHI is based on the hypothesis that when patterns of interaction are active, they are also simultaneously and highly expressed in homogeneous cell populations. We also model the autocrine and paracrine signalling effects of L-R partners

Details

Please have a look at the vignette for a in-depth introduction to the package.


scTHI_plotCluster

Description

Graphs the output of scTHI_runTsne, labeling cells by clusters.

Usage

scTHI_plotCluster(scTHIresult, cexPoint = 0.8, legendPos = c("topleft",
  "topright", "bottomright", "bottomleft"))

Arguments

scTHIresult

scTHI object.

cexPoint

Set the point size.

legendPos

Character string to custom the legend position.

Value

None

Examples

library(scTHI.data)
data(scExample)
result <-  scTHI_score(scExample,
                       cellCusterA = colnames(scExample)[1:30],
                       cellCusterB = colnames(scExample)[31:100],
                       cellCusterAName = "ClusterA",
                       cellCusterBName = "ClusterB", filterCutoff = 0,
                       pvalueCutoff = 1, nPermu = 100, ncore = 8)
result <- scTHI_runTsne(result)
scTHI_plotCluster(result)

scTHI_plotPairs

Description

Generates a plot on the t-SNE coordinates to show the expression levels of an interaction pair of interest. Each cell is colored according to the corresponding gene expression value.

Usage

scTHI_plotPairs(scTHIresult, cexPoint = 0.8, interactionToplot)

Arguments

scTHIresult

scTHI object.

cexPoint

Set the point size.

interactionToplot

Interaction pair to plot.

Value

None

Examples

library(scTHI.data)
data(scExample)
result <-  scTHI_score(scExample,
                 cellCusterA = colnames(scExample)[1:30],
                 cellCusterB = colnames(scExample)[31:100],
                 cellCusterAName = "ClusterA",
                 cellCusterBName = "ClusterB", filterCutoff = 0,
                 pvalueCutoff = 1, nPermu = 100, ncore = 8)
result <- scTHI_runTsne(result)
scTHI_plotPairs(result,interactionToplot = "CXCL12_CD4")

scTHI_plotResult

Description

Creates barplots of scTHI_score results.

Usage

scTHI_plotResult(scTHIresult, cexNames = 0.8, plotType = c("score",
  "pair"), nRes = NULL)

Arguments

scTHIresult

scTHI object.

cexNames

Size of names in barplot.

plotType

Type of plot to be generated. Default is "score", can be also "pair". The "score" option will generate a barplot for each resulted interaction pair, representing the calculated interaction score and the related p-Value.The "pair" option will generate two barplot for each resulted interaction pair, representing the percentage of cells of each cluster expressing partnerA and partnerB gene, respectively.

nRes

Number of pairs to plot (all if NULL).

Value

None

Examples

library(scTHI.data)
data(scExample)
result <-  scTHI_score(scExample,
                       cellCusterA = colnames(scExample)[1:30],
                       cellCusterB = colnames(scExample)[31:100],
                       cellCusterAName = "ClusterA",
                       cellCusterBName = "ClusterB", filterCutoff = 0,
                       pvalueCutoff = 1, nPermu = 100, ncore = 8)

scTHI_plotResult(result, plotType = "score")
scTHI_plotResult(result, plotType = "pair")

scTHI_runTsne

Description

Runs t-SNE dimensionality reduction on selected features based on Rtsne package.

Usage

scTHI_runTsne(scTHIresult)

Arguments

scTHIresult

scTHI object.

Value

The same object as scTHI_score with a fifth item tsneData (data.frame)

Examples

library(scTHI.data)
data(scExample)
result <-  scTHI_score(scExample,
                       cellCusterA = colnames(scExample)[1:30],
                       cellCusterB = colnames(scExample)[31:100],
                       cellCusterAName = "ClusterA",
                       cellCusterBName = "ClusterB", filterCutoff = 0,
                       pvalueCutoff = 1, nPermu = 100, ncore = 8)
result <- scTHI_runTsne(result)

scTHI_score

Description

This function allows the user to compute a score for a set of ligand-receptor pairs, from a single cell gene expression matrix, and detect specific Tumor-Host interactions. You must specify at least two clusters of cells (for example tumor cells and immune cells).

Usage

scTHI_score(expMat, cellCusterA, cellCusterB, cellCusterAName,
  cellCusterBName, topRank = 10, autocrineEffect = TRUE,
  fileNameBase = "scTHI", filterCutoff = 0.5, PValue = TRUE,
  pvalueCutoff = 0.05, nPermu = 1000, ncore = 8)

Arguments

expMat

ScRNA-seq gene expression matrix where rows are genes presented with Hugo Symbols and columns are cells. Gene expression values should be counts or normalized counts.

cellCusterA

Vector of columns of expMat that belong to the first cluster.

cellCusterB

Vector of columns of expMat that belong to the second cluster.

cellCusterAName

A character string labeling the clusterA.

cellCusterBName

A character string labeling the clusterB.

topRank

Filter threshold. Set to 10 (default) means that each gene of the interaction pair will be considered as expressed in a cell if it's in the top rank 10 percent.

autocrineEffect

if TRUE remove the paracrine filter

fileNameBase

Project name.

filterCutoff

Score threshold (default is 0.50). For each interaction pair, if the score calculated (for the partnerA or partnerB) will be less than filterCutoff the interaction pair will be discarded.

PValue

Logical, set to TRUE (default) compute statistical iterations. If p.value < 0.05, the value will be returned.

pvalueCutoff

cutoff of the p-value

nPermu

Number of iterations to perform (default is 1000).

ncore

Number of processors to use.

Value

A list of results, with four items: result (data.frame), expMat (matrix), clusterA (character), clusterA (character)

Examples

####################### example of scTHI_score
library(scTHI.data)
data(scExample)
result <-  scTHI_score(scExample,
      cellCusterA = colnames(scExample)[1:30],
      cellCusterB = colnames(scExample)[31:100],
      cellCusterAName = "ClusterA",
      cellCusterBName = "ClusterB", filterCutoff = 0,
     pvalueCutoff = 1, nPermu = 100, ncore = 8)

TME_classification

Description

The function allows the user to classify non-tumor cells in tumor microenvironment. It implements the Mann-Whitney-Wilcoxon Gene Set Test (MWW-GST) algorithm and tests for each cell the enrichment of a collection of signatures of different cell types.

Usage

TME_classification(expMat, minLenGeneSet = 10,
  alternative = "two.sided", pvalFilter = FALSE, fdrFilter = TRUE,
  pvalCutoff = 0.01, nesCutoff = 0.58, nNES = 1)

Arguments

expMat

Gene expression matrix where rows are genes presented with Hugo Symbols and columns are cells. Gene expression values should be normalized counts.

minLenGeneSet

Minimum gene set length

alternative

a character string specifying the alternative hypothesis of wilcoxon test, must be one of "two.sided" (default), "greater" or "less".

pvalFilter

Logical, if TRUE results will be filtered for p-Value. Defoult is FALSE.

fdrFilter

Logical, if TRUE results will be filtered for FDR.

pvalCutoff

Numeric p-Value (or FDR) threshold. Gene set with p-Value (or FDR) greater than pvalCutoff will be discarded (default is 0.01).

nesCutoff

Numeric threshold. Gene set with NES greater than nesCutoff will be discarded (default is 0.58)

nNES

Default is 0.58, so each cell is classified with a specific phenotype based on the first significant enriched gene set.

Value

A list with two items: Class (character) and ClassLegend (character)

Examples

library(scTHI.data)
data(scExample)
Class <- TME_classification(scExample)

TME_plot

Description

Generates a plot on the t-SNE coordinates, labeling cells by TME classification.

Usage

TME_plot(tsneData, Class, cexPoint = 0.8)

Arguments

tsneData

X and y coordinates of points in the plot.

Class

Object returned by TME_classification function.

cexPoint

Set the point size.

Value

None

Examples

library(scTHI.data)
data(scExample)
result <-  scTHI_score(scExample,
           cellCusterA = colnames(scExample)[1:30],
           cellCusterB = colnames(scExample)[31:100],
           cellCusterAName = "ClusterA",
           cellCusterBName = "ClusterB", filterCutoff = 0,
           pvalueCutoff = 1, nPermu = 100, ncore = 8)
result <- scTHI_runTsne(result)
Class <- TME_classification(scExample)
TME_plot(tsneData = result$tsneData, Class)