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wwylab / TmS

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TmS

Cancer transcriptomes vary greatly. Single-cell RNA sequencing shows that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, impede at-scale pan-cancer examination of total mRNA content. We propose to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimable through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patients across 15 cancer types identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. Cancer-specific patterns of gene alterations, intra-tumor genetic heterogeneity, as well as pan-cancer trends in metabolic dysregulation contribute to TmS. Taken together, our results suggest that measuring cell type-specific total mRNA expression offers an unique perspective on cancer transcriptomes, with biological and clinical implications [1].

We provide a tutorial for TmS, please click here. We have also launched a ShinyApp with all existing TmS values and their corresponding gene expression data across >6,000 cancer patients, feel free to explore the biological correlates of TmS across cancers over here.

Package installation

We used DeMixT v1.2.2 to calculate the TmS values provided in our current study [1]. The DeMixT source files are compatible with Windows, Linux and MacOS. For further information about DeMixT, please visit https://github.com/wwylab/DeMixT.

Install DeMixT

git clone https://github.com/wwylab/DeMixT.git
cd DeMixT
R CMD INSTALL DeMixT_1.2.2.tar.gz

Check if DeMixT is installed successfully:

# load package
library(DeMixT)

Install OpenMP

DeMixT requires OpenMP to enable the parallel computing. We provide a brief instruction for installing OpenMP. Please check the file https://github.com/wwylab/DeMixT/raw/master/HowtoinstallOpenMP.docx.

More information

Please visit the TmS resource page for tutorial and data.

Contact

For questions or support related to the inquiries of TmS, please contact Dr. Wenyi Wang (wwang7@mdanderson.org).

Cite TmS

[1] Cao, S. et al. Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression. Nat Biotechnol (2022). https://doi.org/10.1038/s41587-022-01342-x.