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Xiao Chen edited this page Sep 10, 2020 · 5 revisions

deplink

Author: Xiao Chen

Columbia University Medical Center

Abstract

'deplink' compares the genetic/epigenetic features between cancer cell lines with highest and lowest dependencies of a gene set (signature).

Dependencies

library(cowplot)
library(data.table)
library(ggplot2)
library(ggpubr)
library(ggrepel)
library(purrr)
library(wesanderson)

Install deplink

##  Install deplink in R (>= 3.5.0)
library(devtools)
install_github("seanchen607/deplink")

Load deplink and data libraries

Data source: DepMap (release 2019q4) and CCLE

## load package
library(deplink)

## load data libraries
source(system.file("script", "load_libs.R", package = "deplink"))

All-in-one analysis

For example, deplink compares the genetic/epigenetic features between cancer cell lines with highest and lowest dependencies of "9-1-1" complex members:

deplink(signature.name = "9-1-1", signature = c("RAD9A", "RAD1", "HUS1", "RAD17"))

The results will be output to a local directory (default: root directory) under a folder in name of the designated "signature.name" ("9-1-1" in this case).

Several cutoffs are set by default as below and can be changed by will. Please see the help page for more details (?deplink).

cutoff.freq        = 10
cutoff.percentile  = 0.2
cutoff.pvalue      = 0.05
cutoff.qvalue      = 0.1
cutoff.diff        = 0.1
cutoff.fc          = 2

The comparison covers the following features:

  • Genomic/epigenetic features

    • Genetic dependency
    • Gene expression
    • Chromatin modification

  • Genome instability

    • Genetic mutation
    • COSMIC signature
    • Tumor mutation burden (TMB)
    • Copy number variation (CNV)
    • Microsatellite instability (MSI)

  • Drug sensitivity

    • Drug sensitivity from GDSC data set
    • Drug sensitivity from PRISM data set

  • Immune infiltration

    • Immune signature gene (ISG)

  • Stemness

    • mRNA stemness index (mRNAsi)
    • Epithelial–mesenchymal transition (EMT)

  • Misc.

    • Cancer type

Individual analysis

deplink can compare individual genetic/epigenetic feature between cancer cell lines with highest and lowest dependencies of a gene set (signature). For example of "9-1-1" complex members:

## "9-1-1" complex members as a gene set (signature)
signature.name = "9-1-1"
signature = c("RAD9A", "RAD1", "HUS1", "RAD17")

Cancer type component

'cancertypeHigh' displays the cancer type component of cell lines with high dependencies of a gene set (signature).

## display the cancer type component of cell lines with high dependencies of "9-1-1" complex
cancertypeHigh(signature.name, signature)

'cancertypeLow' displays the cancer type component of cell lines with low dependencies of a gene set (signature).

## display the cancer type component of cell lines with low dependencies of "9-1-1" complex
cancertypeLow(signature.name, signature)

'cancertypeLandscape' displays the landscape of cancer type component of cell lines with different dependencies of a gene set (signature).

## display the landscape of cancer type component of cell lines with different dependencies of "9-1-1" complex
cancertypeLandscape(signature.name, signature)

Genetic dependency

'dependency' compares the genetic dependency between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the genetic dependency between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
dependency(signature.name, signature)

Gene expression

'expressions' compares the gene expression between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the gene expression between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
expressions(signature.name, signature)

Chromatin modification

'chromatinModification' compares the chromatin modification abundance between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the chromatin modification abundance between cell lines with highest and lowest dependencies of "9-1-1" complex
chromatinModification(signature.name, signature)

Genetic mutation

'mutations' compares the genetic mutations between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the genetic mutations between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
mutations(signature.name, signature)

COSMIC signature

'cosmic' compares the COSMIC signatures between cell lines with highest and lowest dependencies of a gene set (signature).

## compare the COSMIC signatures between cell lines with highest and lowest dependencies of "9-1-1" complex
cosmic(signature.name, signature)

Tumor mutation burden (TMB)

'tmb' compares the tumor mutation burden (TMB) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the tumor mutation burden (TMB) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
tmb(signature.name, signature)

Copy number variation (CNV)

'cnv' compares the copy number variation (CNV) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the copy number variation (CNV) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
cnv(signature.name, signature)

Microsatellite instability (MSI)

'msi' compares the microsatellite instability (MSI) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the microsatellite instability (MSI) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
msi(signature.name, signature)

Drug sensitivity

'drugGDSC' compares the drug sensitivity (GDSC dataset) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the drug sensitivity (GDSC dataset) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
drugGDSC(signature.name, signature)

'drugPRISM' compares the drug sensitivity (PRISM dataset) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the drug sensitivity (PRISM dataset) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
drugPRISM(signature.name, signature)

Immune signature gene (ISG)

'isg' compares the immune signature gene (ISG) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the immune signature gene (ISG) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
isg(signature.name, signature)

mRNA stemness index (mRNAsi)

'mrnasi' compares the mRNA stemness index (mRNAsi) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the mRNA stemness index (mRNAsi) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
mrnasi(signature.name, signature)

Epithelial–mesenchymal transition (EMT)

'emt' compares the epithelial–mesenchymal transition (EMT) between cancer cell lines with highest and lowest dependencies of a gene set (signature).

## compare the epithelial–mesenchymal transition (EMT) between cancer cell lines with highest and lowest dependencies of "9-1-1" complex
emt(signature.name, signature)

Citation

If you use deplink in published research, please cite the most appropriate paper(s) from this list:

  1. X Chen, J McGuire, F Zhu, X Xu, Y Li, D Karagiannis, R Dalla-Favera, A Ciccia, J Amengual & C Lu (2020). Harnessing genetic dependency correlation network to reveal chromatin vulnerability in cancer. In preparation.

Session Information

Here is the output of sessionInfo() on the system on which this document was compiled:

sessionInfo()
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