epiregulon.extra

GeneRegulation
R
MIT + file LICENSE

Gene regulatory networks model the underlying gene regulation hierarchies that drive gene expression and observed phenotypes. Epiregulon infers TF activity in single cells by constructing a gene regulatory network (regulons). This is achieved through integration of scATAC-seq and scRNA-seq data and incorporation of public bulk TF ChIP-seq data. Links between regulatory elements and their target genes are established by computing correlations between chromatin accessibility and gene expressions.

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Integrating an increasing number of available multi-omics cancer data remains one of the main challenges to improve our understanding of cancer. One of the main challenges is using multi-omics data for identifying novel cancer driver genes. We have developed an algorithm, called AMARETTO, that integrates copy number, DNA methylation and gene expression data to identify a set of driver genes by analyzing cancer samples and connects them to clusters of co-expressed genes, which we define as modules. We applied AMARETTO in a pancancer setting to identify cancer driver genes and their modules on multiple cancer sites. AMARETTO captures modules enriched in angiogenesis, cell cycle and EMT, and modules that accurately predict survival and molecular subtypes. This allows AMARETTO to identify novel cancer driver genes directing canonical cancer pathways.

SPICEY (SPecificity Index for Coding and Epigenetic activitY) is an R package designed to quantify cell-type specificity in single-cell transcriptomic and epigenomic data, particularly scRNA-seq and scATAC-seq. It introduces two complementary indices: the Gene Expression Tissue Specificity Index (GETSI) and the Regulatory Element Tissue Specificity Index (RETSI), both based on entropy to provide continuous, interpretable measures of specificity. By integrating gene expression and chromatin accessibility, SPICEY enables standardized analysis of cell-type-specific regulatory programs across diverse tissues and conditions.

RNA degradation is monitored through measurement of RNA abundance after inhibiting RNA synthesis. This package has functions and example scripts to facilitate (1) data normalization, (2) data modeling using constant decay rate or time-dependent decay rate models, (3) the evaluation of treatment or genotype effects, and (4) plotting of the data and models. Data Normalization: functions and scripts make easy the normalization to the initial (T0) RNA abundance, as well as a method to correct for artificial inflation of Reads per Million (RPM) abundance in global assessments as the total size of the RNA pool decreases. Modeling: Normalized data is then modeled using maximum likelihood to fit parameters. For making treatment or genotype comparisons (up to four), the modeling step models all possible treatment effects on each gene by repeating the modeling with constraints on the model parameters (i.e., the decay rate of treatments A and B are modeled once with them being equal and again allowing them to both vary independently). Model Selection: The AICc value is calculated for each model, and the model with the lowest AICc is chosen. Modeling results of selected models are then compiled into a single data frame. Graphical Plotting: functions are provided to easily visualize decay data model, or half-life distributions using ggplot2 package functions.

Linnorm is an algorithm for normalizing and transforming RNA-seq, single cell RNA-seq, ChIP-seq count data or any large scale count data. It has been independently reviewed by Tian et al. on Nature Methods (https://doi.org/10.1038/s41592-019-0425-8). Linnorm can work with raw count, CPM, RPKM, FPKM and TPM.

This package provides the necessary functions for performing the Partial Correlation coefficient with Information Theory (PCIT) (Reverter and Chan 2008) and Regulatory Impact Factors (RIF) (Reverter et al. 2010) algorithm. The PCIT algorithm identifies meaningful correlations to define edges in a weighted network and can be applied to any correlation-based network including but not limited to gene co-expression networks, while the RIF algorithm identify critical Transcription Factors (TF) from gene expression data. These two algorithms when combined provide a very relevant layer of information for gene expression studies (Microarray, RNA-seq and single-cell RNA-seq data).

Algorithms for functional network analysis. Includes an implementation of a variational Dirichlet process Gaussian mixture model for nonparametric mixture modeling.