SIMD

High-throughput single-cell measurements of DNA methylomes can quantify methylation heterogeneity and uncover its role in gene regulation. However, technical limitations and sparse coverage can preclude this task. scMET is a hierarchical Bayesian model which overcomes sparsity, sharing information across cells and genomic features to robustly quantify genuine biological heterogeneity. scMET can identify highly variable features that drive epigenetic heterogeneity, and perform differential methylation and variability analyses. We illustrate how scMET facilitates the characterization of epigenetically distinct cell populations and how it enables the formulation of novel hypotheses on the epigenetic regulation of gene expression.

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.

`muscat` provides various methods and visualization tools for DS analysis in multi-sample, multi-group, multi-(cell-)subpopulation scRNA-seq data, including cell-level mixed models and methods based on aggregated “pseudobulk” data, as well as a flexible simulation platform that mimics both single and multi-sample scRNA-seq data.

A tool for unsupervised clustering and analysis of single cell RNA-Seq data.

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.

CATALYST provides tools for preprocessing of and differential discovery in cytometry data such as FACS, CyTOF, and IMC. Preprocessing includes i) normalization using bead standards, ii) single-cell deconvolution, and iii) bead-based compensation. For differential discovery, the package provides a number of convenient functions for data processing (e.g., clustering, dimension reduction), as well as a suite of visualizations for exploratory data analysis and exploration of results from differential abundance (DA) and state (DS) analysis in order to identify differences in composition and expression profiles at the subpopulation-level, respectively.