thonzik/sc-unveil

Splatter is a package for the simulation of single-cell RNA sequencing count data. It provides a simple interface for creating complex simulations that are reproducible and well-documented. Parameters can be estimated from real data and functions are provided for comparing real and simulated datasets.

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.

Like all gene expression data, single-cell data suffers from batch effects and other unwanted variations that makes accurate biological interpretations difficult. The scMerge method leverages factor analysis, stably expressed genes (SEGs) and (pseudo-) replicates to remove unwanted variations and merge multiple single-cell data. This package contains all the necessary functions in the scMerge pipeline, including the identification of SEGs, replication-identification methods, and merging of single-cell data.

Methods to infer clonal tree configuration for a population of cells using single-cell RNA-seq data (scRNA-seq), and possibly other data modalities. Methods are also provided to assign cells to inferred clones and explore differences in gene expression between clones. These methods can flexibly integrate information from imperfect clonal trees inferred based on bulk exome-seq data, and sparse variant alleles expressed in scRNA-seq data. A flexible beta-binomial error model that accounts for stochastic dropout events as well as systematic allelic imbalance is used.

netSmooth is an R package for network smoothing of single cell RNA sequencing data. Using bio networks such as protein-protein interactions as priors for gene co-expression, netsmooth improves cell type identification from noisy, sparse scRNAseq data.

Our scLANE model uses truncated power basis spline models to build flexible, interpretable models of single cell gene expression over pseudotime or latent time. The modeling architectures currently supported are Negative-binomial GLMs, GEEs, & GLMMs. Downstream analysis functionalities include model comparison, dynamic gene clustering, smoothed counts generation, gene set enrichment testing, & visualization.