The goal of GAC is to deliver a formal end-to-end analysis by integrating proven methods of quantitative genetics, statistics, and evolutionary biology for the genetic analysis of single-cell DNA copy number. GAC implements a simple, lightweight, and open-source R framework (Figure 1). Inspired, but unlike Seurat and Scanpy, adapts the logic of espressioSet/AnnData into relational matrices in native R. This keeps the toolkit easy to learn, hard to master; and facilitates the integration of algorithms for the downstream analysis of single-cell DNA data wich is so desperately needed. For now GAC facilitates the downstream analyses of segmented data with common segments by concurrently managing the X, Y across all cells or samples e.g. the output of Varbin/Ginkgo, FACETS, MUMdex, HMMcopy, or SCOPE. The unsegmented bin read counts is not a correct input. GAC uses ComplexHeatmap, an ultra-powerful tool for heatmaps to help visualize the data.
To implement GAC we require five easy to generate inputs: - a copy number / genotype matrix (X) (bins[i] x cells[j]) - a phenotype matrix (Y) (cells[j] x phenotype[y]) - a qc matrix (technical wet-lab notes) (qc) (cells[j] x qc[c]) - a gene to bin index (gene.index) - the genomic coordinates of the bins or genotypes (chromInfo) - and an optional expression matrix (Ye; for DNA-RNA or same-cell G+T(Macaulay, et al.2015)
install.packages("devtools") devtools::install_github("KrasnitzLab/SCclust") install.packages("BiocManager") BiocManager::install(c("ComplexHeatmap", "ConsensusClusterPlus"))
You can install the development version from GitHub with:
This is a basic example for drawing a copy number heatmap. For a
comprehensive overview of the package please follow the
getting_started.Rmd in the
library(gac) ## basic example code data(cnr) data(segCol) data(legSeg) ( excl.cells <- rownames(cnr$qc)[cnr$qc$qc.status == "FAIL"] ) #>  "cell5" "cell11" cnr <- excludeCells(cnr, excl = excl.cells) aH <- HeatmapCNR(cnr, what = 'X', col = segCol, show_heatmap_legend = FALSE) draw(aH, annotation_legend_list = list(legSeg))
bH <- HeatmapCNR(cnr, what = "genes", which.genes = c("CDK4", "MDM2"), col = segCol, show_heatmap_legend = FALSE) #> Warning: The input is a data frame, convert it to the matrix. draw(bH, annotation_legend_list = list(legSeg))
binand the .X should be a matrix of common
binsfor all cells. However, to make biological sense of the data, gene level resolution is required. Thus, building a syncronized matrix with genes is of outmost importance. At the 11th hour, having a gene to bin index (gene.index) allowed the flexibility to interpolate the bin data to gene level resolution and integration to the complete set of phenotypes, and QC data, but it’s not the restricted to the mouse mouse or human genomes. Cows, viruses, and plants have genomes too!
The Singer Lab single-cell wet-lab and dry-lab endevours are carried forward by a skeleton crew. The need to have something simple that can help reduce the 85% of the time spent syncronizing bins, to genes, to phenotypes, and QC matrices capable of handling a large data set of >24,000 cells was greatly needed. Knowing the data is growing by the week, I integrated functions to deal with the n+1 problem. Lastly, my background in animal genomics allowed me to borrow the succesful frameworks used in Genomic Selection in an abstract way in hopes that we can provide appropriate models for future same-cell technologies.
We hope you enjoy !
Integration of Henderson’s Animal Model for the phenoype-genotype analyses
Integration with MLR for non-linear genetic models
Integration with CORE and GISTIC2 for fidning focal and recurrent events
Integration of infScite for somatic alteration evolution
Integration with Pathview for KEGG pathway visualization
support for .seg files
Cleaner code with tidyverse
GAC framework and code is distributed under a BSD-3 License
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