Package: GRaNIE 1.17.0

Motivation and Necessity | Installation | GRaNIE package and required dependency packages | Additional packages | Detailed information about the scope of the optional packages | Example Workflow | Example GRN object | Input | Open chromatin and RNA-seq data | TF and TFBS data | HOCOMOCO-derived TFBS and download links | Other TFBS sources | Importing TF and TFBS from the JASPAR databases directly in R | Sample metadata (optional but highly recommended) | Hi-C data (optional) | Capture Hi-C data / known promoter-enhancer links (optional) | SNP data (optional) | TF activity data (optional, coming soon) | Methodological Details and Basic Mode of Action | Data normalization | Normalization methods common for peaks and RNA data | Normalization methods specific for peaks data | Raw vs pre.normalized data | TF-peak connections | TF-peak connection types | GC correction | TF Activity connections | Calculating TF Activity | Importing TF Activity | Adding TF Activity TF-peak connections | Peak-gene associations | Building eGRNs: Linking TF-peak and peak-gene links and filtering | Background eGRN | Methods | Object and output details related to the background links | Constructing the eGRN graph | Enrichment analyses | Network visualization and visualization filtering | General comments | Changing the visualization parameters and layout | Filtering the network for visualization purposes | Feature variation quantification | Output | GRN object and results stored within | Object details | Results in the object | Object summary | Original and normalized data, annotations and provided metadata | Object data | Plots | PCA plots and results | TF-peak results and diagnostic plots | Overall connection summary | TF-specific plots | Connection summary | Correlation plots | Extra plots for the GC correction | Overall summary | Activator-repressor classification results and diagnostic plots | Peak-gene results and diagnostic plots | Correlation raw p-value distribution | Correlation coefficient distribution | Stratification with metadata and additional features | Filtered TF-peak-gene connections (eGRN table) | TF-gene connections | Connection summary plots | eGRN graph | Community information | Enrichment results and plots | General enrichment | Community enrichment | TF enrichment | Feature variation quantification | SNP data | Guidelines, Recommendations, Limitations, Scope | Package scope | Number of samples | Peaks | RNA-Seq | Transcription factor binding sites (TFBS) | Choice of correlation methods for TF-peak, peak-gene, TF-gene connections and outlier robustness | Peak-gene p-values accuracy and violations | eGRNs from single-cell data | Recapitulating object history, function parameters etc | Memory footprint and execution time, feasibility with large datasets | CPU time | Memory footprint | References

Motivation and Summary | General notes and sources | Prerequisites: a multimodal Seurat object | Our default preprocessing | RNA | ATAC | Integrating the modalities | Clustering and pseudobulk creation | Methods | Choosing the right number of clusters and working strategies for running GRaNIE | Filtering | Preparing the input data for GRaNIE | Metadata | TF database | Running GRaNIE | Scripts | Data processing and GRaNIE preparation | Current limitations | Example data | Further notes and FAQs | Session Info

Motivation and Summary | Example data | Example Workflow | Install suggested, additional packages for full functionality | Note on version compatibility and errors in the vignette | General notes | Reading the data required for the GRaNIE package | Initialize a GRaNIE object | Add data | Object history | Quality control 1: PCA plots | Add TFs and TFBS and overlap with peak | Filter data (optional) | Add TF-enhancer connections | Quality control 2: Diagnostic plots for TF-enhancer connections | Run the AR classification and QC (optional) | Save GRaNIE object to disk (optional) | Add enhancer-gene connections | Quality control 3: Diagnostic plots for enhancer-gene connections | Combine TF-enhancer and enhancer-gene connections and filter | Add TF-gene correlations (optional) | Retrieve filtered connections | Generate a connection summary for filtered connections | Construct the eGRN graph | Visualize the eGRN | Network and enrichment analyses for filtered connections | General network statistics | General network enrichment | Community network statistics and enrichment | TF enrichment analyses | Wrapping up | How to continue? | Session Info