The point of this package is to calculate the Aneuploidy Score for a chromosomal arm SCNA/aneuploidy (CAA) as detailed in the following two papers:
Shukla, A., Nguyen, T. H., Moka, S. B., Ellis, J. J., Grady, J. P., Oey, H., ... & Duijf, P. H. (2020). Chromosome arm aneuploidies shape tumour evolution and drug response. Nature communications, 11(1), 1-14. (https://doi.org/10.1038/s41467-020-14286-0)
Cohen-Sharir, Y., McFarland, J. M., Abdusamad, M., Marquis, C., Bernhard, S. V., Kazachkova, M., ... & Ben-David, U. (2021). Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition. Nature, 1-6. (https://doi.org/10.1038/s41586-020-03114-6)
Install using
devtools::install_github("quevedor2/aneuploidy_score", ref='master') # Latest stable build
devtools::install_github("quevedor2/aneuploidy_score", ref='dev') # Development branch
A guide for how to use the package can be found at inst/rmd/demo_guide.html
Defintions:
Aneuploidy score (AS): as described by Cohen-Sharir et al., is simply the total number of arm-level gains and losses for a tumor, adjusted for ploidy.
Chromosomal arm-level SCNAs/Aneuploidies (CAA): as described by Shukla et al., are arm-level aneuploidies that are pervasive in cancer and found ~30x higher than expected based on the inverse-length distribution of focal SCNAs.
AS and CAAs are calculated two different ways:
Shukla method:
Cohen-Sharir method:
To have some data to work with, the CCLE 639-V cell line seg file is included in the package, as well as cytobands downloaded from UCSC table browser for:
library(AneuploidyScore)
data("seg")
data("ucsc.hg19.cytoband")
Clump the cytobands into p-arm, q-arm and centromere segments, then split by chromosome:
cytoarm <- cytobandToArm(ucsc.hg19.cytoband)
Estimate the ploidy of your individual sample (this method uses the weighted-mean approach):
tcn_col <- 'TCN'
wgd_ploidy <- checkIfWGD(seg, tcn_col = tcn_col, threshold = 0.5,
wgd_gf = 0.5, ploidy_method = 'wmean')
Using the estimated ploidy, identify the classification of Loss/Neutral/Gain (-1/0/1) for each CN segment (segCNclass) or the Cohen-Sharir's weighted-median chromosome arm (armCNclass).
threshold <- 0.5
seg_caa <- getCAA(seg, cytoarm, tcn_col=tcn_col, classifyCN=TRUE,
ploidy=wgd_ploidy['ploidy'], threshold=threshold)
Reduce the CN-segment specific GRangesList object down to a simplified chromosome-arm representation and calculate the aneuploidy score:
caa <- reduceArms(seg_caa, caa_method=c('arm', 'seg'),
arm_ids = c('p', 'q'))
AS <- colSums(abs(caa), na.rm = TRUE)
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