# R package for TENET (Tracing regulatory Element Networks using Epigenetic Traits) to identify key transcription factors

## Documentation for package ‘TENET’ version 1.0.0

- DESCRIPTION file.
- User guides, package vignettes and other documentation.
- Package NEWS.

## Help Pages

easyTENET | Run the step 1 through step 6 functions with default arguments
humanTranscriptionFactorList | Human transcription factor list
step1MakeExternalDatasets | Create a GRanges object representing putative regulatory element regions, based on the data sources selected for inclusion, to be used in later TENET steps
step2GetDifferentiallyMethylatedSites | Identify differentially methylated RE DNA methylation sites
step3GetAnalysisZScores | Calculate Z-scores comparing the mean expression of each gene in the case samples that are hyper- or hypomethylated for each RE DNA methylation site chosen in step 2
step4SelectMostSignificantLinksPerDNAMethylationSite | Select the most significant RE DNA methylation site-gene links to each RE DNA methylation site
step5OptimizeLinks | Find final RE DNA methylation site-gene links using various optimization metrics
step6DNAMethylationSitesPerGeneTabulation | Tabulate the total number of RE DNA methylation sites linked to each of the genes
step7ExpressionVsDNAMethylationScatterplots | Create scatterplots displaying the expression of the top genes and the methylation levels of each of their linked RE DNA methylation sites, along with copy number variation, somatic mutation, and purity data, if provided by the user
step7LinkedDNAMethylationSiteCountHistograms | Create histograms displaying the number of genes or transcription factors linked to a given number of RE DNA methylation sites
step7LinkedDNAMethylationSitesMotifSearching | Perform motif searching for transcription factor motifs in the vicinity of RE DNA methylation sites linked to the specified transcription factors
step7SelectedDNAMethylationSitesCaseVsControlBoxplots | Generate boxplots comparing the methylation level of the specified RE DNA methylation sites in case and control samples
step7StatesForLinks | Identify which of the case samples harbor each of the identified regulatory element DNA methylation site-gene links
step7TopGenesCaseVsControlExpressionBoxplots | Create boxplots comparing the expression level of the top genes/transcription factors in case and control samples
step7TopGenesCircosPlots | Generate Circos plots displaying the links between top identified genes and each of the RE DNA methylation sites linked to them
step7TopGenesDNAMethylationHeatmaps | Generate heatmaps displaying the methylation level of all RE DNA methylation sites linked to the top genes/transcription factors, along with the expression of those genes in the column headers, in the case samples within the supplied MultiAssayExperiment object
step7TopGenesExpressionCorrelationHeatmaps | Generate mirrored heatmaps displaying the correlation of the expression values of the top genes/TFs
step7TopGenesOverlappingLinkedDNAMethylationSitesHeatmaps | Generate binary heatmaps displaying which of the top genes/transcription factors share links with each of the unique regulatory element DNA methylation sites linked to at least one top gene/TF
step7TopGenesSurvival | Perform Kaplan-Meier and Cox regression analyses to assess the association of top gene expression and linked RE DNA methylation site methylation with patient survival
step7TopGenesTADTables | Create tables using user-supplied topologically associating domain (TAD) information which identify the topologically associating domains containing each RE DNA methylation site linked to the top genes/transcription factors, as well as other genes in the same topologically associating domain as potential downstream targets
step7TopGenesUCSCBedFiles | Create bed-formatted interact files which can be loaded on the UCSC Genome Browser to display links between top genes and transcription factors and their linked RE DNA methylation sites
step7TopGenesUserPeakOverlap | Identify if RE DNA methylation sites linked to top genes/transcription factors are located within a specific distance of specified genomic regions
TCGADownloader | Download TCGA gene expression, DNA methylation, and clinical datasets and compile them into a MultiAssayExperiment object
TENETCacheAllData | Cache all online datasets required by TENET examples and optional features