scRank

Cells respond divergently to drugs due to the heterogeneity among cell populations,thus it is crucial to identify the drug-responsive cell population for accurately elucidating the mechanism of drug action, which is a great challenge yet. Here, we address it with scRank using a target-perturbed gene regulatory network (tpGRN) to rank and infer drug-responsive cell population towards in-silico drug perturbation for single-cell transcriptomic data under disease condition. scRank enables the inference of drug-responsive cell types for single-cell data under disease condition, providing new insights into the mechanism of drug action.

Installation

install dependent packages devtools and rTensor )

#install.packages("devtools")
#devtools::install_github("rikenbit/rTensor")
devtools::install_github("ZJUFanLab/scRank")

Overview

scRank method consists of two components, wherein the first is to reconstruct the gene regulatory network from expression ptrofiles using Constr_net function and the second step is to estimate the effect of the in silico drug perturbation for GRNs in each cell type using rank_celltype function.

scRank start with create a S4 object by CreateScRank function:

the input is the gene expression profil eand meta is the cell type information.
cell_type is the column name of the cell type information in meta
species is the species of the data. ("mouse" or "human")
drug is the drug name and target is the target gene of the drug. drug could be any inhibitor in our database utile_database. if you know the specific target gene of the drug, you can input the target gene into target without inputing drug.

CreateScRank <- function(input,
                         meta,
                         cell_type,
                         species,
                         drug,
                         target)

The format of the input is as follows:

gene expression profile formatted by matrix or data frame, where the column is gene and the row is cell.
Seurat object with metadata containing cell type information

The meta is required if input is not a Seurat objectas, where its format as follows:

a dataframe with row names as cell names matched with column names of input and column names as cell type information cooresponding to the cell_type argument.

Tutorial

In this tutorial, we will demonstrate how to infer the drug-responsive cell type by scRank based on a demo dataset (GSE110894) containing BET inhibitor resistant and sensitive leukaemic cells.

1. Load the data and create a scRank object

we load the demo dataset from Seurat object, the drug target is known as Brd4.

seuratObj <- system.file("extdata", "AML_object.rda", package="scRank")
load(seuratObj)
obj <- CreateScRank(input = seuratObj,
                    species = 'mouse',
                    cell_type = 'labels',
                    target = 'Brd4')

2. Construct the gene regulatory network

obj <- scRank::Constr_net(obj)

3. Rank the cell types

obj <- scRank::rank_celltype(obj)

the final infered rank of cell types that determine the drug response is stored in obj@cell_type_rank

4. Visualize the result

For visulizing the rank of cell types in dimension reduction space, we can use the plot_dim function.

plot_dim(obj)

For visulizing the modularized drug-target-gene related subnetwork in specific cell type, we can use the plot_net function, where the parameter mode can be "heatmap" or "network" for different visualization.

plot_net(obj, mode = "heatmap", cell_type = "sensitive")
plot_net(obj, mode = "heatmap", cell_type = "resistant")

zhongmicai/scRank