metaITH is an R package for analyzing intratumor heterogeneity at the DNA, RNA, and immune levels. Options include a comprehensive signature analysis looking at the anti-PD1, apoptosis, epithelial-mesenchymal, hypoxia, pemetrexed resistance, and proliferation signatures, a dendrogram analysis at the DNA, RNA, and immune levels, and a multiregion divergence and diversity analysis using data at the DNA, RNA, and immune levels.
Must have R version 3.5 or higher
install.packages(devtools) library(devtools) install_packages("sjdlabgroup/metaITH") library(metaITH)
To run metaITH using example datasets, the metaITH package must be downloaded and unzipped. The example datasets are in the folder input_files. To run metaITH using user-provided datasets, the working directory must be set to the folder containing the datasets before using any functions in the package.
To run all functions below simultaneously, use the function
metaITH_analysis("DNA_dendro_list.txt", "RNA_dendro_list.txt", "Immune_dendro_list.txt", "sample_names.txt", "RNA_matrix.txt")
Functions calculate specific signature scores for the anti-PD1, apoptosis, epithelial-mesenchymal, hypoxia, pemetrexed resistance, and proliferation signatures, that calculate all the above signature scores, and that calculate the signature scores for a geneset supplied by the user. All functions also create a heatmap of the scores.
The function that calculate signature scores for a user-specificied signature take as input a matrix of z-scores that can be created by running the function
signature_analysis("RNA_matrix.txt","all") z_score_calculations("RNA_matrix.txt") specified_geneset_signature("z-scores_matrix.txt", "proliferation_signature.txt")
Functions create distance matrices from DNA, RNA, or immune data and use the distance matrices to create unrooted dendrograms using neighbor-joining method, as well as SNV heatmaps.
dna_dendrograms("DNA_dendro_list.txt") rna_dendrograms("RNA_dendro_list.txt") immune_dendrograms("Immune_dendro_list.txt") snv_heatmaps("DNA_dendro_list.txt")
Function provides an estimate of the ratio of intra-patient regional diversity to tumor-benign tissue divergence, using the output of the dendrogram analysis functions.
A. Sharma, E. Merritt, A. Cruz, C. Jiang, H. Sarkodie, Z. Zhou, J. Malhotra, S. De, Non-genetic intra-tumor heterogeneity is a major predictor of phenotypic heterogeneity and ongoing evolutionary dynamics in lung tumors, Bioxriv (2019).
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