HDTD

A collection of methods for performing random rotations on high-dimensional, normally distributed data (e.g. microarray or RNA-seq data) with batch structure. The random rotation approach allows exact testing of dependent test statistics with linear models following arbitrary batch effect correction methods.

BANDITS is a Bayesian hierarchical model for detecting differential splicing of genes and transcripts, via differential transcript usage (DTU), between two or more conditions. The method uses a Bayesian hierarchical framework, which allows for sample specific proportions in a Dirichlet-Multinomial model, and samples the allocation of fragments to the transcripts. Parameters are inferred via Markov chain Monte Carlo (MCMC) techniques and a DTU test is performed via a multivariate Wald test on the posterior densities for the average relative abundance of transcripts.

distinct is a statistical method to perform differential testing between two or more groups of distributions; differential testing is performed via hierarchical non-parametric permutation tests on the cumulative distribution functions (cdfs) of each sample. While most methods for differential expression target differences in the mean abundance between conditions, distinct, by comparing full cdfs, identifies, both, differential patterns involving changes in the mean, as well as more subtle variations that do not involve the mean (e.g., unimodal vs. bi-modal distributions with the same mean). distinct is a general and flexible tool: due to its fully non-parametric nature, which makes no assumptions on how the data was generated, it can be applied to a variety of datasets. It is particularly suitable to perform differential state analyses on single cell data (i.e., differential analyses within sub-populations of cells), such as single cell RNA sequencing (scRNA-seq) and high-dimensional flow or mass cytometry (HDCyto) data. To use distinct one needs data from two or more groups of samples (i.e., experimental conditions), with at least 2 samples (i.e., biological replicates) per group.

DifferentialRegulation is a method for detecting differentially regulated genes between two groups of samples (e.g., healthy vs. disease, or treated vs. untreated samples), by targeting differences in the balance of spliced and unspliced mRNA abundances, obtained from single-cell RNA-sequencing (scRNA-seq) data. From a mathematical point of view, DifferentialRegulation accounts for the sample-to-sample variability, and embeds multiple samples in a Bayesian hierarchical model. Furthermore, our method also deals with two major sources of mapping uncertainty: i) 'ambiguous' reads, compatible with both spliced and unspliced versions of a gene, and ii) reads mapping to multiple genes. In particular, ambiguous reads are treated separately from spliced and unsplced reads, while reads that are compatible with multiple genes are allocated to the gene of origin. Parameters are inferred via Markov chain Monte Carlo (MCMC) techniques (Metropolis-within-Gibbs).

The package contains methods to visualise the expression profile of genes from a microarray or RNA-seq experiment, and offers a supervised clustering approach to identify GO terms containing genes with expression levels that best classify two or more predefined groups of samples. Annotations for the genes present in the expression dataset may be obtained from Ensembl through the biomaRt package, if not provided by the user. The default random forest framework is used to evaluate the capacity of each gene to cluster samples according to the factor of interest. Finally, GO terms are scored by averaging the rank (alternatively, score) of their respective gene sets to cluster the samples. P-values may be computed to assess the significance of GO term ranking. Visualisation function include gene expression profile, gene ontology-based heatmaps, and hierarchical clustering of experimental samples using gene expression data.

This package is intended to identify differentially expressed genes driven by Copy Number Alterations from samples with both gene expression and CNA data.