terapadog

Recent advances in single cell/nucleus transcriptomic technology has enabled collection of cohort-scale datasets to study cell type specific gene expression differences associated disease state, stimulus, and genetic regulation. The scale of these data, complex study designs, and low read count per cell mean that characterizing cell type specific molecular mechanisms requires a user-frieldly, purpose-build analytical framework. We have developed the dreamlet package that applies a pseudobulk approach and fits a regression model for each gene and cell cluster to test differential expression across individuals associated with a trait of interest. Use of precision-weighted linear mixed models enables accounting for repeated measures study designs, high dimensional batch effects, and varying sequencing depth or observed cells per biosample.

A package for inferring, comparing, and visualizing gene networks from single-cell RNA sequencing data. It integrates multiple methods (GENIE3, GRNBoost2, ZILGM, PCzinb, and JRF) for robust network inference, supports consensus building across methods or datasets, and provides tools for evaluating regulatory structure and community similarity. GRNBoost2 requires Python package 'arboreto' which can be installed using init_py(install_missing = TRUE). This package includes adapted functions from ZILGM (Park et al., 2021), JRF (Petralia et al., 2015), and learn2count (Nguyen et al. 2023) packages with proper attribution under GPL-2 license.

Genetic variants associated with diseases often affect non-coding regions, thus likely having a regulatory role. To understand the effects of genetic variants in these regulatory regions, identifying genes that are modulated by specific regulatory elements (REs) is crucial. The effect of gene regulatory elements, such as enhancers, is often cell-type specific, likely because the combinations of transcription factors (TFs) that are regulating a given enhancer have cell-type specific activity. This TF activity can be quantified with existing tools such as diffTF and captures differences in binding of a TF in open chromatin regions. Collectively, this forms a gene regulatory network (GRN) with cell-type and data-specific TF-RE and RE-gene links. Here, we reconstruct such a GRN using single-cell or bulk RNAseq and open chromatin (e.g., using ATACseq or ChIPseq for open chromatin marks) and optionally (Capture) Hi-C data. Our network contains different types of links, connecting TFs to regulatory elements, the latter of which is connected to genes in the vicinity or within the same chromatin domain (TAD). We use a statistical framework to assign empirical FDRs and weights to all links using a permutation-based approach.

markeR is an R package that provides a modular and extensible framework for the systematic evaluation of gene sets as phenotypic markers using transcriptomic data. The package is designed to support both quantitative analyses and visual exploration of gene set behaviour across experimental and clinical phenotypes. It implements multiple methods, including score-based and enrichment approaches, and also allows the exploration of expression behaviour of individual genes. In addition, users can assess the similarity of their own gene sets against established collections (e.g., those from MSigDB), facilitating biological interpretation.

topGO package provides tools for testing GO terms while accounting for the topology of the GO graph. Different test statistics and different methods for eliminating local similarities and dependencies between GO terms can be implemented and applied.

This package provides functionality to run a number of tasks in the differential expression analysis workflow. This encompasses the most widely used steps, from running various enrichment analysis tools with a unified interface to creating plots and beautifying table components linking to external websites and databases. This streamlines the generation of comprehensive analysis reports.