readAlexandrovSignatures takes forever

[komalsrathi]

Hi,

I am trying to run signatures <- decompTumor2Sig::readAlexandrovSignatures() but it seems to be taking forever. I never faced this issue before - have been using the function for quite a few years. Here is my R session:

R version 4.4.0 (2024-04-24)
Platform: aarch64-apple-darwin20
Running under: macOS 15.2

Matrix products: default
BLAS:   /System/Library/Frameworks/Accelerate.framework/Versions/A/Frameworks/vecLib.framework/Versions/A/libBLAS.dylib 
LAPACK: /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/lib/libRlapack.dylib;  LAPACK version 3.12.0

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

time zone: America/New_York
tzcode source: internal

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] decompTumor2Sig_2.22.0 ggplot2_3.5.1         

loaded via a namespace (and not attached):
 [1] KEGGREST_1.44.0                         SummarizedExperiment_1.34.0            
 [3] gtable_0.3.5                            rjson_0.2.21                           
 [5] Biobase_2.64.0                          lattice_0.22-6                         
 [7] vctrs_0.6.5                             tools_4.4.0                            
 [9] bitops_1.0-7                            generics_0.1.3                         
[11] stats4_4.4.0                            curl_5.2.1                             
[13] parallel_4.4.0                          tibble_3.2.1                           
[15] fansi_1.0.6                             AnnotationDbi_1.65.2                   
[17] RSQLite_2.3.6                           blob_1.2.4                             
[19] pkgconfig_2.0.3                         Matrix_1.7-0                           
[21] data.table_1.15.4                       BSgenome_1.72.0                        
[23] S4Vectors_0.42.0                        readxl_1.4.3                           
[25] lifecycle_1.0.4                         GenomeInfoDbData_1.2.12                
[27] compiler_4.4.0                          Rsamtools_2.20.0                       
[29] Biostrings_2.72.0                       munsell_0.5.1                          
[31] codetools_0.2-20                        GenomeInfoDb_1.40.0                    
[33] RCurl_1.98-1.14                         yaml_2.3.8                             
[35] TxDb.Hsapiens.UCSC.hg19.knownGene_3.2.2 pillar_1.9.0                           
[37] crayon_1.5.2                            BiocParallel_1.38.0                    
[39] cachem_1.0.8                            DelayedArray_0.30.0                    
[41] abind_1.4-5                             tidyselect_1.2.1                       
[43] VariantAnnotation_1.50.0                dplyr_1.1.4                            
[45] restfulr_0.0.15                         fastmap_1.1.1                          
[47] rprojroot_2.0.4                         grid_4.4.0                             
[49] colorspace_2.1-2                        cli_3.6.2                              
[51] BSgenome.Hsapiens.UCSC.hg19_1.4.3       SparseArray_1.4.0                      
[53] magrittr_2.0.3                          S4Arrays_1.4.0                         
[55] GenomicFeatures_1.56.0                  XML_3.99-0.16.1                        
[57] utf8_1.2.4                              withr_3.0.2                            
[59] scales_1.3.0                            UCSC.utils_1.0.0                       
[61] bit64_4.0.5                             XVector_0.44.0                         
[63] httr_1.4.7                              matrixStats_1.3.0                      
[65] bit_4.0.5                               gridExtra_2.3                          
[67] cellranger_1.1.0                        png_0.1-8                              
[69] memoise_2.0.1                           GenomicRanges_1.55.4                   
[71] IRanges_2.38.0                          BiocIO_1.14.0                          
[73] rtracklayer_1.64.0                      rlang_1.1.4                            
[75] Rcpp_1.0.12                             glue_1.8.0                             
[77] DBI_1.2.2                               BiocGenerics_0.50.0                    
[79] rstudioapi_0.16.0                       jsonlite_1.8.8                         
[81] plyr_1.8.9                              R6_2.5.1                               
[83] ggseqlogo_0.2                           MatrixGenerics_1.16.0                  
[85] GenomicAlignments_1.40.0                zlibbioc_1.50.0                        

[komalsrathi]

The issue is with this line that was introduced in the recent versions:

while(sum(sigVec) != 1) {  # once wasn't always sufficient!
                sigVec <- sigVec/sum(sigVec)
            }

The loop just keeps going on and on...

[rmpiro]

Dear Komal,

that's strange. Could you let me have the signature data file that you're trying to load?
You can write to: [email protected]

This way I can try to replicate the problem.

Thanks!

[komalsrathi]

Sure, thanks for replying. I'll send it shortly.

[komalsrathi]

Actually, I am trying to load the default COSMIC signatures i.e. just running readAlexandrovSignatures without any input. I think the default is https://cancer.sanger.ac.uk/cancergenome/assets/signatures_probabilities.txt. The command below takes forever to run:

signatures <- decompTumor2Sig::readAlexandrovSignatures()

However, when I replace the while statement with just sigVec <- sigVec/sum(sigVec), it seems to work fine.

[rmpiro]

Dear Komal,

That is very strange, the default works perfectly fine for me. If I remember well, the default does actually not require the normalization and it was a later version where the signature vectors didn't add up to precisely 1. But I'm not 100% sure here.

In any case: this default is the old version 2 of the COSMIC mutational signatures. It might anyway be better to use the newest version (SBS signatures v3.4) downloaded from the COSMIC website: https://cancer.sanger.ac.uk/signatures/downloads/

Can you please test whether these work for you? Thanks!

[komalsrathi]

I just tested this but taking forever i.e. never finishes:

library(decompTumor2Sig)
signatures <- readAlexandrovSignatures(file = "~/Downloads/COSMIC_v3.4_SBS_GRCh38.txt")

It is indeed weird. I can't think of anything else but could be some issue with my package version or a dependency? In either case, if you are able to run it fine, then it is something on my end so I will close this. In the meanwhile, I will continue to use it by commenting out the while statement. Thanks for checking!