StatescopeR

Provides an interface to infer the parameters of BASiCS using the variational inference (ADVI), Markov chain Monte Carlo (NUTS), and maximum a posteriori (BFGS) inference engines in the Stan programming language. BASiCS is a Bayesian hierarchical model that uses an adaptive Metropolis within Gibbs sampling scheme. Alternative inference methods provided by Stan may be preferable in some situations, for example for particularly large data or posterior distributions with difficult geometries.

Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels in seemingly homogeneous populations of cells. However, these experiments are prone to high levels of technical noise, creating new challenges for identifying genes that show genuine heterogeneous expression within the population of cells under study. BASiCS (Bayesian Analysis of Single-Cell Sequencing data) is an integrated Bayesian hierarchical model to perform statistical analyses of single-cell RNA sequencing datasets in the context of supervised experiments (where the groups of cells of interest are known a priori, e.g. experimental conditions or cell types). BASiCS performs built-in data normalisation (global scaling) and technical noise quantification (based on spike-in genes). BASiCS provides an intuitive detection criterion for highly (or lowly) variable genes within a single group of cells. Additionally, BASiCS can compare gene expression patterns between two or more pre-specified groups of cells. Unlike traditional differential expression tools, BASiCS quantifies changes in expression that lie beyond comparisons of means, also allowing the study of changes in cell-to-cell heterogeneity. The latter can be quantified via a biological over-dispersion parameter that measures the excess of variability that is observed with respect to Poisson sampling noise, after normalisation and technical noise removal. Due to the strong mean/over-dispersion confounding that is typically observed for scRNA-seq datasets, BASiCS also tests for changes in residual over-dispersion, defined by residual values with respect to a global mean/over-dispersion trend.

RETROFIT is a Bayesian non-negative matrix factorization framework to decompose cell type mixtures in ST data without using external single-cell expression references. RETROFIT outperforms existing reference-based methods in estimating cell type proportions and reconstructing gene expressions in simulations with varying spot size and sample heterogeneity, irrespective of the quality or availability of the single-cell reference. RETROFIT recapitulates known cell-type localization patterns in a Slide-seq dataset of mouse cerebellum without using any single-cell data.

A differential abundance analysis for the comparison of two or more conditions. Useful for analyzing data from standard RNA-seq or meta-RNA-seq assays as well as selected and unselected values from in-vitro sequence selections. Uses a Dirichlet-multinomial model to infer abundance from counts, optimized for three or more experimental replicates. The method infers biological and sampling variation to calculate the expected false discovery rate, given the variation, based on a Wilcoxon Rank Sum test and Welch's t-test (via aldex.ttest), a Kruskal-Wallis test (via aldex.kw), a generalized linear model (via aldex.glm), or a correlation test (via aldex.corr). All tests report predicted p-values and posterior Benjamini-Hochberg corrected p-values. ALDEx2 also calculates expected standardized effect sizes for paired or unpaired study designs. ALDEx2 can now be used to estimate the effect of scale on the results and report on the scale-dependent robustness of results.

Low- and high-level wrappers for Gemma's RESTful API. They enable access to curated expression and differential expression data from over 10,000 published studies. Gemma is a web site, database and a set of tools for the meta-analysis, re-use and sharing of genomics data, currently primarily targeted at the analysis of gene expression profiles.

BLASE is a method for finding where bulk RNA-seq data lies on a single-cell pseudotime trajectory. It uses a fast and understandable approach based on Spearman correlation, with bootstrapping to provide confidence. BLASE can be used to "date" bulk RNA-seq data, annotate cell types in scRNA-seq, and help correct for developmental phenotype differences in bulk RNA-seq experiments.