SuperCell

Coarse-graining of large single-cell RNA-seq data into metacells

https://github.com/gfellerlab/supercell

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Coarse-graining of large single-cell RNA-seq data into metacells

README.Rmd

---
title: "Coarse-graining of large single-cell RNA-seq data into metacells"
csl: elsevier-harvard.csl
output:
  md_document:
    variant: markdown_github
---

```{r, echo = FALSE}
knitr::opts_chunk$set(
  collapse = TRUE,
  fig.path = "plots/"
)
```

[![R-CMD-check](https://github.com/GfellerLab/SuperCell/workflows/R-CMD-check/badge.svg)](https://github.com/GfellerLab/SuperCell/actions)
[![DOI](https://img.shields.io/badge/DOI%3A-10.1186/s12859--022--04861--1-brightgreen)](https://doi.org/10.1186/s12859-022-04861-1)
[![License](https://img.shields.io/badge/License-LICENSE-green)](./LICENSE)


# Coarse-graining of large single-cell RNA-seq data into metacells
SuperCell is an R package for coarse-graining large single-cell RNA-seq data into metacells and performing downstream analysis at the metacell level. 

The exponential scaling of scRNA-seq data represents an important hurdle for downstream analyses.
One of the solutions to facilitate the analysis of large-scale and noisy scRNA-seq data is to merge transcriptionally highly similar cells into *metacells*. This concept was first introduced by [*Baran et al., 2019*](https://doi.org/10.1186/s13059-019-1812-2) (MetaCell) and by [*Iacono et al., 2018*](https://doi:10.1101/gr.230771.117) (bigSCale). More recent methods to build *metacells* have been described in [*Ben-Kiki et al. 2022*](https://doi.org/10.1186/s13059-022-02667-1) (MetaCell2), [*Bilous et al., 2022*](https://doi.org/10.1186/s12859-022-04861-1) (SuperCell) and [*Persad et al., 2022*](https://doi.org/10.1038/s41587-023-01716-9) (SEACells). Despite some differences in the implementation, all the methods are network-based and can be summarized as follows: 

**1.** A single-cell network is computed based on cell-to-cell similarity (in transcriptomic space)

**2.** Highly similar cells are identified as those forming dense regions in the single-cell network and merged together into metacells (coarse-graining)

**3.** Transcriptomic information within each metacell is combined (average or sum).

**4.** Metacell data are used for the downstream analyses instead of large-scale single-cell data

```{r echo=FALSE}
knitr::include_graphics("plots/Fig1A.png")
```

Unlike clustering, the aim of metacells is not to identify large groups of cells that comprehensively capture biological concepts, like cell types, but to merge cells that share highly similar profiles, and may carry repetitive information. **Therefore metacells represent a compromise structure that optimally remove redundant information in scRNA-seq data while preserving the biologically relevant heterogeneity.**

An important concept when building metacells is the **graining level** (*γ*), which we define as the ratio between the number of single cells in the initial data and the number of metacells. We suggest applying *γ* between $10$ and $50$, which significantly reduces the computational resources needed to perform the downstream analyses while preserving most of the result of the initial (i.e., single-cell) analyses.


## Installation

SuperCell requires [igraph](https://cran.r-project.org/web/packages/igraph/index.html), [RANN](https://cran.r-project.org/web/packages/RANN/index.html), [WeightedCluster](https://cran.r-project.org/web/packages/WeightedCluster/index.html), [corpcor](https://cran.r-project.org/web/packages/corpcor/index.html), [weights](https://cran.r-project.org/web/packages/weights/index.html), [Hmisc](https://cran.r-project.org/web/packages/Hmisc/index.html), [Matrix](https://cran.r-project.org/web/packages/Matrix/index.html), [matrixStats](https://cran.rstudio.com/web/packages/matrixStats/index.html), [plyr](https://cran.r-project.org/web/packages/plyr/index.html), [irlba](https://cran.r-project.org/web/packages/irlba/index.html), 
[grDevices](https://stat.ethz.ch/R-manual/R-devel/library/grDevices/html/00Index.html),
[patchwork](https://cran.r-project.org/web/packages/patchwork/index.html),
[ggplot2](https://cloud.r-project.org/web/packages/ggplot2/index.html).
SuperCell uses [velocyto.R](https://github.com/velocyto-team/velocyto.R) for RNA velocity.



```{r install imported packages, eval=FALSE}
install.packages("igraph")
install.packages("RANN")
install.packages("WeightedCluster")
install.packages("corpcor")
install.packages("weights")
install.packages("Hmisc")
install.packages("Matrix")
install.packages("patchwork")
install.packages("plyr")
install.packages("irlba")
```

Installing SuperCell package from gitHub

```{r library, eval=FALSE}
if (!requireNamespace("remotes")) install.packages("remotes")
remotes::install_github("GfellerLab/SuperCell")

library(SuperCell)
```

## Examples

1. [Building and analyzing metacells with SuperCell](./vignettes/a_SuperCell.Rmd)
2. [RNA velocity applied to SuperCell object](./vignettes/c_RNAvelocity_for_SuperCell.Rmd)
3. [Building metacells with SuperCell and alayzing them with a standard Seurat pipeline](https://github.com/GfellerLab/SIB_workshop/blob/main/workbooks/Workbook_1__cancer_cell_lines.md)
4. [Data integration of metacells built with SuperCell](https://github.com/GfellerLab/SIB_workshop/blob/main/workbooks/Workbook_2__COVID19_integration.md)

## [License](./LICENSE)

SuperCell is developed by the group of David Gfeller at University of Lausanne.

SuperCell can be used freely by academic groups for non-commercial purposes under the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0) (see [license](./LICENSE)). 
The product is provided free of charge, and, therefore, on an "as is" basis, without warranty of any kind.

FOR-PROFIT USERS

If you plan to use SuperCell or any data provided with the script in any for-profit application, you are required to obtain a separate license. 
To do so, please contact Nadette Bulgin [nbulgin\@licr.org](mailto:nbulgin@licr.org) at the Ludwig Institute for Cancer Research Ltd.

If required, FOR-PROFIT USERS are also expected to have proper licenses for the tools used in SuperCell, including the R packages igraph, RANN, WeightedCluster, corpora, weights, Hmisc, Matrix, ply, irlba, grDevices, patchwork, ggplot2 and velocyto.R

For scientific questions, please contact Mariia Bilous ([mariia.bilous\@unil.ch](mailto:mariia.bilous@unil.ch)) or David Gfeller ([David.Gfeller\@unil.ch](mailto:David.Gfeller@unil.ch)).

## How to cite

If you use SuperCell in a publication, please cite: [Bilous et al. Metacells untangle large and complex single-cell transcriptome networks, BMC Bioinformatics (2022).](https://doi.org/10.1186/s12859-022-04861-1)

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