1 Introduction

Cancer-Testis (CT) genes, also called Cancer-Germline (CG), are a group of genes whose expression is normally restricted to the germline but that are found aberrantly activated in many types of cancers. These genes produce cancer specific antigens represent ideal targets for anti-cancer vaccines. Besides their interest in immunotherapy, they can also be used as cancer biomarkers and as target of anti-tumor therapies with limited side effect.

Many CT genes use DNA methylation as a primary mechanism of transcriptionnal regulation. This is another interesting point about CT genes as they represent suitable models to study DNA demethylation in cancer.

Currently the reference database gathering CT genes is the CTdatabase that was published in 2009, based on a literature screening(Almeida et al., 2009). This database is however not up to date. Recently identified CT genes are not referenced (in particular CT genes identified by omics methods that didn’t exist at the time) while some genes referred as CT genes appeared to be in reality expressed in many somatic tissues. Furthermore, the database is not in an easily importable format, some genes are not encoded properly (by synonyms names rather than by their official HGNC symbol names, or by a concatenation of both) resulting in poor interoperability for downstream analyses. More recent studies proposed other lists of CT genes like Wang’s CTatlas (Wang et al., 2016, Jamin et al., 2021, Carter et al., 2023). These lists were established using different criteria to define CT genes and hence differ substantially from each other. Moreover, these lists are usually provided as supplemental data files and are not strictly speaking databases. Finally, none of these studies describe the involvement of DNA methylation in the regulation of individual CT genes.

We therefore created CTexploreR, a Bioconductor R package, aimed to redefine rigorously the list of CT genes based on publicly available RNAseq databases and to summarize their main characteristics. We included methylation analyses to classify these genes according to whether they are regulated or not by DNA methylation. The package also offers tools to visualize CT genes expression and promoter DNA methylation in normal and tumoral tissues. CTexploreR hence represents an up-to-date reference database for CT genes and can be used as a starting point for further investigations related to these genes.

2 Installation

To install the package:

if (!require("BiocManager")) {
    install.packages("BiocManager")
}

BiocManager::install("CTexploreR")

To install the package from GitHub:

if (!require("BiocManager")) {
    install.packages("BiocManager")
}

BiocManager::install("UCLouvain-CBIO/CTexploreR")

3 CT genes

The central element of CTexploreR is the list of 280 CT and CTP genes (see table below) selected based on their expression in normal and tumoral tissues (selection details in the next section). The table also summarises their main characteristics.

library(CTexploreR)
## Loading required package: CTdata
head(CT_genes, 10)

CTdata is the companion Package for CTexploreR and provides the omics data that was necessary to select and characterize cancer testis genes as well as exploring them. The data are served through the ExperimentHub infrastructure. Currently available data are summarised in the table below and details can be found in CTdata vignette or manuals.

CTdata()

4 CT gene selection

In order to generate the list of CT genes, we followed a specific selection procedure (see figure below).