cbaf

TENET identifies key transcription factors (TFs) and regulatory elements (REs) linked to a specific cell type by finding significantly correlated differences in gene expression and RE DNA methylation between case and control input datasets, and identifying the top genes by number of significant RE DNA methylation site links. It also includes many tools for visualization and analysis of the results, including plots displaying and comparing methylation and expression data and methylation site link counts, survival analysis, TF motif searching in the vicinity of linked RE DNA methylation sites, custom TAD and peak overlap analysis, and UCSC Genome Browser track file generation. A utility function is also provided to download methylation, expression, and patient survival data from The Cancer Genome Atlas (TCGA) for use in TENET or other analyses.

Data analysis, linear models and differential expression for omics data.

Differential expression analysis of sequence count data. Implements a range of statistical methodology based on the negative binomial distributions, including empirical Bayes estimation, exact tests, generalized linear models, quasi-likelihood, and gene set enrichment. Can perform differential analyses of any type of omics data that produces read counts, including RNA-seq, ChIP-seq, ATAC-seq, Bisulfite-seq, SAGE, CAGE, metabolomics, or proteomics spectral counts. RNA-seq analyses can be conducted at the gene or isoform level, and tests can be conducted for differential exon or transcript usage.

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.

pathwayPCA is an integrative analysis tool that implements the principal component analysis (PCA) based pathway analysis approaches described in Chen et al. (2008), Chen et al. (2010), and Chen (2011). pathwayPCA allows users to: (1) Test pathway association with binary, continuous, or survival phenotypes. (2) Extract relevant genes in the pathways using the SuperPCA and AES-PCA approaches. (3) Compute principal components (PCs) based on the selected genes. These estimated latent variables represent pathway activities for individual subjects, which can then be used to perform integrative pathway analysis, such as multi-omics analysis. (4) Extract relevant genes that drive pathway significance as well as data corresponding to these relevant genes for additional in-depth analysis. (5) Perform analyses with enhanced computational efficiency with parallel computing and enhanced data safety with S4-class data objects. (6) Analyze studies with complex experimental designs, with multiple covariates, and with interaction effects, e.g., testing whether pathway association with clinical phenotype is different between male and female subjects. Citations: Chen et al. (2008) <https://doi.org/10.1093/bioinformatics/btn458>; Chen et al. (2010) <https://doi.org/10.1002/gepi.20532>; and Chen (2011) <https://doi.org/10.2202/1544-6115.1697>.

This package implements a variety of functions useful for gene set analysis using rotations to approximate the null distribution. It contributes with the implementation of seven test statistic scores that can be used with different goals and interpretations. Several functions are available to complement the statistical results with graphical representations.