Error in YAPSA::annotate_intermut_dist_cohort
1
1
Entering edit mode
TRASA • 0
@trasa-17881
Last seen 5.5 years ago

Hi

I tried to use the annotateintermutdist_cohort command from the YAPSA package on my VRangesList. However, I got following error message.i

> vr_dist <- annotate_intermut_dist_cohort(vrl, in_mode="min", in_verbose = TRUE)
Error in `[[<-`(`*tmp*`, name, value = c(1e+10, 248956422, 18778245, 4036160,  : 
  1049 elements in value to replace 464 elements

I went through the source code, but I could not really figure out what this error means and how I could solve it. Maybe I did something wrong when I generated the VRanges List. I have a list of vcf files that I combined in one VRangesList:

for (i in 1:length(list_vcf))
{
  vr = c(vr, readVcfAsVRanges(list_vcf[i], ref_genome, ScanVcfParam(geno=NA)))
}

(geno=NA because I have a few variants with AD<0 that I excluded that way)

  names(vr) <- sample_names
   vrl <- VRangesList(vr)
   vrl
  VRangesList of length 252

Has anyone experienced the same error message? (In case you can suggest a more elegent way how to genertae the VRangesList, feel free to help as well)

session info()
R version 3.5.1 (2018-07-02)
Platform: x86_64-apple-darwin15.6.0 (64-bit)
Running under: macOS  10.14.4

Matrix products: default
BLAS: /System/Library/Frameworks/Accelerate.framework/Versions/A/Frameworks/vecLib.framework/Versions/A/libBLAS.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRlapack.dylib

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

attached base packages:
 [1] grid      stats4    parallel  stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] SomaticSignatures_2.18.0          NMF_0.21.0                        cluster_2.0.9                     rngtools_1.3.1                   
 [5] pkgmaker_0.27                     registry_0.5-1                    VariantAnnotation_1.28.13         Rsamtools_1.34.1                 
 [9] SummarizedExperiment_1.12.0       DelayedArray_0.8.0                BiocParallel_1.16.6               matrixStats_0.54.0               
[13] BSgenome.Hsapiens.UCSC.hg38_1.4.1 BSgenome_1.50.0                   rtracklayer_1.42.2                YAPSA_1.8.0                      
[17] bigmemory_4.5.33                  Biobase_2.42.0                    ggplot2_3.1.1                     GenomicRanges_1.34.0             
[21] GenomeInfoDb_1.18.2               Biostrings_2.50.2                 XVector_0.22.0                    IRanges_2.16.0                   
[25] S4Vectors_0.20.1                  BiocGenerics_0.28.0              

loaded via a namespace (and not attached):
  [1] bigmemory.sri_0.1.3      colorspace_1.4-1         rjson_0.2.20             biovizBase_1.30.1        circlize_0.4.6          
  [6] htmlTable_1.13.1         GlobalOptions_0.1.0      base64enc_0.1-3          dichromat_2.0-0          proxy_0.4-23            
 [11] rstudioapi_0.10          bit64_0.9-7              AnnotationDbi_1.44.0     codetools_0.2-16         splines_3.5.1           
 [16] ggbio_1.30.0             doParallel_1.0.14        lsei_1.2-0               knitr_1.23               Formula_1.2-3           
 [21] gridBase_0.4-7           png_0.1-7                graph_1.60.0             BiocManager_1.30.4       compiler_3.5.1          
 [26] httr_1.4.0               backports_1.1.4          assertthat_0.2.1         Matrix_1.2-17            lazyeval_0.2.2          
 [31] acepack_1.4.1            htmltools_0.3.6          prettyunits_1.0.2        tools_3.5.1              gtable_0.3.0            
 [36] glue_1.3.1               GenomeInfoDbData_1.2.0   reshape2_1.4.3           dplyr_0.8.1              PMCMR_4.3               
 [41] Rcpp_1.0.1               iterators_1.0.10         xfun_0.7                 stringr_1.4.0            ensembldb_2.6.8         
 [46] XML_3.98-1.19            dendextend_1.12.0        zlibbioc_1.28.0          scales_1.0.0             pcaMethods_1.74.0       
 [51] hms_0.4.2                ProtGenerics_1.14.0      RBGL_1.58.2              AnnotationFilter_1.6.0   RColorBrewer_1.1-2      
 [56] ComplexHeatmap_1.20.0    yaml_2.2.0               curl_3.3                 memoise_1.1.0            gridExtra_2.3           
 [61] biomaRt_2.38.0           rpart_4.1-15             reshape_0.8.8            latticeExtra_0.6-28      stringi_1.4.3           
 [66] RSQLite_2.1.1            corrplot_0.84            foreach_1.4.4            checkmate_1.9.3          GenomicFeatures_1.34.8  
 [71] bibtex_0.4.2             shape_1.4.4              rlang_0.3.4              pkgconfig_2.0.2          bitops_1.0-6            
 [76] lattice_0.20-38          purrr_0.3.2              GenomicAlignments_1.18.1 htmlwidgets_1.3          bit_1.1-14              
 [81] tidyselect_0.2.5         GGally_1.4.0             plyr_1.8.4               magrittr_1.5             R6_2.4.0                
 [86] Hmisc_4.2-0              DBI_1.0.0                pillar_1.4.1             foreign_0.8-71           withr_2.1.2             
 [91] survival_2.44-1.1        KEGGREST_1.22.0          RCurl_1.95-4.12          nnet_7.3-12              tibble_2.1.2            
 [96] crayon_1.3.4             OrganismDbi_1.24.0       viridis_0.5.1            GetoptLong_0.1.7         progress_1.2.2          
[101] data.table_1.12.2        blob_1.1.1               digest_0.6.19            xtable_1.8-4             munsell_0.5.0           
[106] viridisLite_0.3.0        gtrellis_1.14.0
YAPSA • 1.0k views
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Entering edit mode
Marc • 0
@2f4b9c03
Last seen 17 months ago
Germany

BUG

The error arises in the annotate_intermut_dist_PID function called inside annotate_intermut_dist_cohort:

> suppressPackageStartupMessages(library("YAPSA"))
> suppressPackageStartupMessages(library("VariantAnnotation"))
> 
> test_vr <-
+   VRanges(
+     seqnames = paste0("chr",c(1, 1, 1,2,2,2,3,3,3,4, 4, 4, 4,  5,  5)),
+     ranges =                c(1,20,40,4,6,9,1,4,8,1,10,35,40,100,200),
+     ref = c("C","C","C","T","T","T","A","A","A","G","G","G","G","N","A"),
+     alt = c("A","G","T","A","C","G","C","G","T","A","C","C","T","A","N"),
+     refDepth = NA,
+     altDepth = NA,
+     totalDepth = NA,
+     sampleNames = NA,
+     hardFilters = FilterRules(),
+     softFilterMatrix = NA,
+     tumorSpecific = NA )
> min_dist_vr <-
+   annotate_intermut_dist_PID(
+     test_vr,
+     in_CHROM.field = "CHROM",
+     in_POS.field = "POS",
+     in_mode = "min")
Error in `[[<-`(`*tmp*`, name, value = c(1e+10, 19, 3, 1, 2, 2, 3, 8,  : 
  12 elements in value to replace 15 elements

and is caused by the output of the GenomicRanges::gaps function in:

[...]
    if(inherits(in_dat, "VRanges")) {
        in_dat$dist1 <- c(1e10, as.numeric(width(gaps(in_dat)))[-1])
        in_dat$dist2 <- c(as.numeric(width(gaps(in_dat)))[-1], 1e10)
        out_dat$dist <- apply(mcols(in_dat)[,c("dist1","dist2")], 1, min)
    }
[...]

I assume the output of GenomicRanges::gaps changed at some point because the current output doesn't fit the application it is used in here.

FIX

To obtain the desired output, the function could be adapted to:

annotate_intermut_dist_PID <- function(in_dat, in_CHROM.field = "CHROM",
                                        in_POS.field = "POS", in_mode = "min",
                                        in_verbose = FALSE){
    out_dat <- in_dat
    # account for input data type
    if(inherits(in_dat, "VRanges")) {
        in_dat$dist1 <- c( 1e10, distance( in_dat[-length(in_dat)], in_dat[-1] ) + 1 )
        in_dat$dist2 <- c( distance( in_dat[-1], in_dat[-length(in_dat)] ) + 1, 1e10)
        out_dat$dist <- apply( mcols(in_dat)[,c("dist1","dist2")], 1, min, na.rm = TRUE )
    } else if(inherits(in_dat, "data.frame")){
        CHROM_ind <- which(names(in_dat)==in_CHROM.field)
        POS_ind <- which(names(in_dat)==in_POS.field)
        inflate_df <- data.frame()
        for(my_chrom in unique(in_dat[,CHROM_ind])) {
            my_df <- in_dat[which(in_dat[,CHROM_ind]==my_chrom),]
            region_df <- data.frame(start=my_df[,POS_ind],end=my_df[,POS_ind])
        if(dim(my_df)[1]<2) {
            temp_df <- region_df
            temp_df$dist <- c(100000000)
        } else {
            temp_df <- circlize::rainfallTransform(region_df, mode = in_mode)
        }
        temp_df$CHROM <- my_chrom
        inflate_df <- rbind(inflate_df,temp_df)
    }
    out_dat$dist <- inflate_df[,dim(inflate_df)[2]-1]
    } else {
        if(in_verbose) cat("YAPSA:::annotate_intermut_dist_PID::error: input",
                " data is neither of type VRanges nor data.frame")
        return(NULL)
    }
    return(out_dat)
}

EXAMPLE

This produces the same output as for a data frame list:

> test_df <-
+   data.frame(
+     CHROM = paste0("chr",c(1, 1, 1,2,2,2,3,3,3,4, 4, 4, 4,  5,  5)),
+     POS =                c(1,20,40,4,6,9,1,4,8,1,10,35,40,100,200),
+     REF = c("C","C","C","T","T","T","A","A","A","G","G","G","G","N","A"),
+     ALT = c("A","G","T","A","C","G","C","G","T","A","C","C","T","A","N") )
> min_dist_df <-
+   annotate_intermut_dist_PID(
+     test_df,
+     in_CHROM.field = "CHROM",
+     in_POS.field = "POS",
+     in_mode = "min")
> 
> test_vr <-
+   VRanges(
+     seqnames = paste0("chr",c(1, 1, 1,2,2,2,3,3,3,4, 4, 4, 4,  5,  5)),
+     ranges =                c(1,20,40,4,6,9,1,4,8,1,10,35,40,100,200),
+     ref = c("C","C","C","T","T","T","A","A","A","G","G","G","G","N","A"),
+     alt = c("A","G","T","A","C","G","C","G","T","A","C","C","T","A","N"),
+     refDepth = NA,
+     altDepth = NA,
+     totalDepth = NA,
+     sampleNames = NA,
+     hardFilters = FilterRules(),
+     softFilterMatrix = NA,
+     tumorSpecific = NA )
> min_dist_vr <-
+   annotate_intermut_dist_PID(
+     test_vr,
+     in_CHROM.field = "CHROM",
+     in_POS.field = "POS",
+     in_mode = "min")
> 
> min_dist_df
   CHROM POS REF ALT dist
1   chr1   1   C   A   19
2   chr1  20   C   G   19
3   chr1  40   C   T   20
4   chr2   4   T   A    2
5   chr2   6   T   C    2
6   chr2   9   T   G    3
7   chr3   1   A   C    3
8   chr3   4   A   G    3
9   chr3   8   A   T    4
10  chr4   1   G   A    9
11  chr4  10   G   C    9
12  chr4  35   G   C    5
13  chr4  40   G   T    5
14  chr5 100   N   A  100
15  chr5 200   A   N  100
> as.data.frame(min_dist_vr)[,c(1,2,6,7,14)]
   seqnames start ref alt dist
1      chr1     1   C   A   19
2      chr1    20   C   G   19
3      chr1    40   C   T   20
4      chr2     4   T   A    2
5      chr2     6   T   C    2
6      chr2     9   T   G    3
7      chr3     1   A   C    3
8      chr3     4   A   G    3
9      chr3     8   A   T    4
10     chr4     1   G   A    9
11     chr4    10   G   C    9
12     chr4    35   G   C    5
13     chr4    40   G   T    5
14     chr5   100   N   A  100
15     chr5   200   A   N  100

INTERMUTATION DISTANCE

The real question to me is whether the intermutation distance should be the distance to the closest (as implemented) or previous variant. The latter is how I would interpret the definition from Nik-Zainal et al. 2012:

[...] the intermutation distance, the distance between each somatic substitution, and the substitution immediately before it [...]

This behavior would best be approximated by:

[...]
    if(inherits(in_dat, "VRanges")) {
      out_dat$dist <- c( NA, distance( in_dat[-length(in_dat)], in_dat[-1] ) + 1 )
    }
[...]

and wouldn't lead to duplicated distances (e.g. see chr4), but would lead to missing distances at the start of each contig:

> test_vr <-
+   VRanges(
+     seqnames = paste0("chr",c(1, 1, 1,2,2,2,3,3,3,4, 4, 4, 4,  5,  5)),
+     ranges =                c(1,20,40,4,6,9,1,4,8,1,10,35,40,100,200),
+     ref = c("C","C","C","T","T","T","A","A","A","G","G","G","G","N","A"),
+     alt = c("A","G","T","A","C","G","C","G","T","A","C","C","T","A","N"),
+     refDepth = NA,
+     altDepth = NA,
+     totalDepth = NA,
+     sampleNames = NA,
+     hardFilters = FilterRules(),
+     softFilterMatrix = NA,
+     tumorSpecific = NA )
> prev_dist_vr <-
+   annotate_intermut_dist_PID(
+     test_vr,
+     in_CHROM.field = "CHROM",
+     in_POS.field = "POS",
+     in_mode = "min")
> 
> as.data.frame(min_dist_vr)[,c(1,2,6,7,14)]
   seqnames start ref alt dist
1      chr1     1   C   A   19
2      chr1    20   C   G   19
3      chr1    40   C   T   20
4      chr2     4   T   A    2
5      chr2     6   T   C    2
6      chr2     9   T   G    3
7      chr3     1   A   C    3
8      chr3     4   A   G    3
9      chr3     8   A   T    4
10     chr4     1   G   A    9
11     chr4    10   G   C    9
12     chr4    35   G   C    5
13     chr4    40   G   T    5
14     chr5   100   N   A  100
15     chr5   200   A   N  100
> as.data.frame(prev_dist_vr)[,c(1,2,6,7,14)]
   seqnames start ref alt dist
1      chr1     1   C   A   NA
2      chr1    20   C   G   19
3      chr1    40   C   T   20
4      chr2     4   T   A   NA
5      chr2     6   T   C    2
6      chr2     9   T   G    3
7      chr3     1   A   C   NA
8      chr3     4   A   G    3
9      chr3     8   A   T    4
10     chr4     1   G   A   NA
11     chr4    10   G   C    9
12     chr4    35   G   C   25
13     chr4    40   G   T    5
14     chr5   100   N   A   NA
15     chr5   200   A   N  100
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SESSION INFO

R version 4.1.3 (2022-03-10)
Platform: x86_64-conda-linux-gnu (64-bit)
Running under: CentOS Linux 7 (Core)

Matrix products: default
BLAS/LAPACK: /home/ruebsam/.conda/envs/bioconductor_yapsa/lib/libopenblasp-r0.3.20.so

locale:
[1] C

attached base packages:
[1] grid      stats4    stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] VariantAnnotation_1.40.0    Rsamtools_2.10.0            Biostrings_2.62.0           XVector_0.34.0              SummarizedExperiment_1.24.0 MatrixGenerics_1.6.0        matrixStats_0.62.0          YAPSA_1.19.0               
 [9] Biobase_2.54.0              ggplot2_3.3.6               GenomicRanges_1.46.1        GenomeInfoDb_1.30.0         IRanges_2.28.0              S4Vectors_0.32.3            BiocGenerics_0.40.0        

loaded via a namespace (and not attached):
  [1] backports_1.4.1                   circlize_0.4.15                   Hmisc_4.7-0                       corrplot_0.92                     NMF_0.21.0                        BiocFileCache_2.2.0              
  [7] plyr_1.8.7                        lazyeval_0.2.2                    splines_4.1.3                     BiocParallel_1.28.3               gridBase_0.4-7                    gtrellis_1.26.0                  
 [13] digest_0.6.29                     foreach_1.5.2                     ensembldb_2.18.1                  htmltools_0.5.2                   viridis_0.6.2                     fansi_1.0.3                      
 [19] magrittr_2.0.3                    checkmate_2.1.0                   memoise_2.0.1                     BSgenome_1.62.0                   cluster_2.1.3                     doParallel_1.0.17                
 [25] ComplexHeatmap_2.10.0             limSolve_1.5.6                    ggbio_1.42.0                      lpSolve_5.6.15                    prettyunits_1.1.1                 jpeg_0.1-9                       
 [31] colorspace_2.0-3                  blob_1.2.3                        rappdirs_0.3.3                    xfun_0.31                         dplyr_1.0.9                       tcltk_4.1.3                      
 [37] crayon_1.5.1                      RCurl_1.98-1.6                    graph_1.72.0                      SomaticSignatures_2.30.0          survival_3.3-1                    iterators_1.0.14                 
 [43] glue_1.6.2                        registry_0.5-1                    gtable_0.3.0                      zlibbioc_1.40.0                   GetoptLong_1.0.5                  DelayedArray_0.20.0              
 [49] shape_1.4.6                       scales_1.2.0                      rngtools_1.5.2                    DBI_1.1.2                         GGally_2.1.2                      Rcpp_1.0.8.3                     
 [55] xtable_1.8-4                      viridisLite_0.4.0                 progress_1.2.2                    htmlTable_2.4.0                   clue_0.3-60                       proxy_0.4-26                     
 [61] foreign_0.8-82                    bit_4.0.4                         OrganismDbi_1.36.0                PMCMR_4.4                         Formula_1.2-4                     htmlwidgets_1.5.4                
 [67] httr_1.4.3                        RColorBrewer_1.1-3                ellipsis_0.3.2                    pkgconfig_2.0.3                   reshape_0.8.9                     XML_3.99-0.9                     
 [73] nnet_7.3-17                       dbplyr_2.2.0                      utf8_1.2.2                        tidyselect_1.1.2                  rlang_1.0.2                       reshape2_1.4.4                   
 [79] AnnotationDbi_1.56.1              munsell_0.5.0                     tools_4.1.3                       cachem_1.0.6                      cli_3.3.0                         generics_0.1.2                   
 [85] RSQLite_2.2.8                     stringr_1.4.0                     fastmap_1.1.0                     yaml_2.3.5                        knitr_1.39                        bit64_4.0.5                      
 [91] purrr_0.3.4                       KEGGREST_1.34.0                   AnnotationFilter_1.18.0           dendextend_1.15.2                 RBGL_1.70.0                       pracma_2.3.8                     
 [97] xml2_1.3.3                        biomaRt_2.50.0                    compiler_4.1.3                    rstudioapi_0.13                   beeswarm_0.4.0                    filelock_1.0.2                   
[103] curl_4.3.2                        png_0.1-7                         tibble_3.1.7                      stringi_1.7.6                     GenomicFeatures_1.46.1            lattice_0.20-45                  
[109] ProtGenerics_1.26.0               Matrix_1.4-1                      vctrs_0.4.1                       pillar_1.7.0                      lifecycle_1.0.1                   BiocManager_1.30.18              
[115] GlobalOptions_0.1.2               data.table_1.14.2                 bitops_1.0-7                      rtracklayer_1.54.0                pcaMethods_1.86.0                 R6_2.5.1                         
[121] BiocIO_1.4.0                      latticeExtra_0.6-29               gridExtra_2.3                     vipor_0.4.5                       codetools_0.2-18                  dichromat_2.0-0.1                
[127] MASS_7.3-57                       assertthat_0.2.1                  pkgmaker_0.32.2                   rjson_0.2.21                      withr_2.5.0                       GenomicAlignments_1.30.0         
[133] GenomeInfoDbData_1.2.7            parallel_4.1.3                    hms_1.1.1                         quadprog_1.5-8                    rpart_4.1.16                      BSgenome.Hsapiens.UCSC.hg19_1.4.3
[139] biovizBase_1.42.0                 base64enc_0.1-3                   ggbeeswarm_0.6.0                  restfulr_0.0.14
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It has to be noted that the example fix requires the VRanges object to be ordered by CHROM and POS.

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