ERROR: there was a problem in the initial guess of the polynomial

[KamilMaliszArdigen]

Hi Thank you for this tool we are trying to use to for our dataset and we are getting following error:

Output and error:

  ..Reading mappability for chromosome Un_KI270746v1
  skipping chromosome Un_KI270746v1
  ..Reading mappability for chromosome Un_KI270747v1
  skipping chromosome Un_KI270747v1
  ..Reading mappability for chromosome Un_KI270748v1
  skipping chromosome Un_KI270748v1
  ..Reading mappability for chromosome Un_KI270749v1
  skipping chromosome Un_KI270749v1
  ..Reading mappability for chromosome Un_KI270750v1
  skipping chromosome Un_KI270750v1
  ..Reading mappability for chromosome Un_KI270751v1
  skipping chromosome Un_KI270751v1
  ..Reading mappability for chromosome Un_KI270752v1
  skipping chromosome Un_KI270752v1
  ..Reading mappability for chromosome Un_KI270753v1
  skipping chromosome Un_KI270753v1
  ..Reading mappability for chromosome Un_KI270754v1
  skipping chromosome Un_KI270754v1
  ..Reading mappability for chromosome Un_KI270755v1
  skipping chromosome Un_KI270755v1
  ..Reading mappability for chromosome Un_KI270756v1
  skipping chromosome Un_KI270756v1
  ..Reading mappability for chromosome Un_KI270757v1
  skipping chromosome Un_KI270757v1
  ..Reading mappability for chromosome Un_GL000214v1
  skipping chromosome Un_GL000214v1
  ..Reading mappability for chromosome Un_KI270742v1
  skipping chromosome Un_KI270742v1
  ..Reading mappability for chromosome Un_GL000216v2
  skipping chromosome Un_GL000216v2
  ..Reading mappability for chromosome Un_GL000218v1
  skipping chromosome Un_GL000218v1
  ..Reading mappability for chromosome X
  ..Control: Last window: from 144475606 to 156030895
  ..Reading mappability for chromosome Y
  skipping chromosome Y
  ..Reading mappability for chromosome Y_KI270740v1_random
  skipping chromosome Y_KI270740v1_random
  ..file out100m2_hg38.gem is read
  ..Mappability profile was taken into account for 23 chromosomes
  ..432 chromosomes were skipped
  CG-content printed into ./GC_profile.targetedRegions.cnp
  ..Mappability track from out100m2_hg38.gem has been added to ./GC_profile.targetedRegions.cnp
  ..using GC-content to normalize the control profile
  file ./GC_profile.targetedRegions.cnp is read
  ..will remove all windows with read count in the control less than 50
  ..will process the control file as well: removing all windows with read count in the control less than 50
  ..Set ploidy for the control genome equal to 2
  ..Running FREEC with ploidy set to 2
  ERROR: there was a problem in the initial guess of the polynomial. Please contact the support team of change your input parameters. Exit.

config:

[general]
BedGraphOutput = TRUE
chrFiles =/home/j/work/2b/7bc1ada518b63963e5a81d3c1d4793/Chromsomes
chrLenFile = /home/j/work/2b/7bc1ada518b63963e5a81d3c1d4793/Homo_sapiens_assembly38.len
coefficientOfVariation = 0.05
degree = 1
forceGCcontentNormalization = 1
gemMappabilityFile = /home/j/work/2b/7bc1ada518b63963e5a81d3c1d4793/out100m2_hg38.gem
minimalSubclonePresence = 30
maxThreads = 2
noisyData = TRUE
ploidy = 2
printNA = FALSE
readCountThreshold = 50
sex = XX

[control]
mateFile = /home/j/work/2b/7bc1ada518b63963e5a81d3c1d4793/WGC035467D_vs_WGC035466D.normal.mpileup.gz
inputFormat = pileup
mateOrientation = FR

[sample]
mateFile = /home/j/work/2b/7bc1ada518b63963e5a81d3c1d4793/WGC035467D_vs_WGC035466D.tumor.mpileup.gz
inputFormat = pileup
mateOrientation = FR

[BAF]
fastaFile = /home/j/work/2b/7bc1ada518b63963e5a81d3c1d4793/Homo_sapiens_assembly38.fasta
SNPfile = /home/j/work/2b/7bc1ada518b63963e5a81d3c1d4793/dbsnp_146.hg38.vcf.gz

[target]
captureRegions = wgs_calling_regions_noseconds.hg38.bed

Do you see any mistakes in config which can cause this error?

[valeu]

Hi, is it WGS data?

If it is targeted sequencing (e.g. exome-seq), please try removing these two lines from your config:

degree = 1
forceGCcontentNormalization = 1

[KamilMaliszArdigen]

We have WES data. We will test your suggestion and let you know.
Thank you very much for quick reply

[bkalinowskamajka-ardigen]

Hi Valentina, thank you for your reply. I have modified the config file according to your suggestion but the same error was returned. Do you see any other parameters that we could modify to execute the tool successfully on these samples?

[valeu]

Could you please the complete output into the command line together with the config file? Thank you!

[bkalinowskamajka-ardigen]

Hi, I am working on the same data as @KamilMaliszArdigen.

Please see the config file:
config.txt

and the command output (split by Nextflow into command.log and command.err files):
command_log.txt
command_err.txt

[emilyhuntsman]

Hi I'm wondering if there was ever a resolution to this issue, I'm also running with WES data and getting the exact same error. Thank you so much! (using nextflow sarek)

[valeu]

I am not not 100% sure that it was the problem, but I would change
mateOrientation = FR
to
mateOrientation = 0

because FREEC cannot guess the orientation of paired reads from pileups.

[valeu]

But in the previous case the problem was clearly in the target region file. From the log:

..Reading wgs_calling_regions_noseconds.hg38.bed
Number of exons analysed in chromosome 1 : 15
Average exon length in chromosome 1 : 1.53658e+07

and so on.
How can one target just 15 regions on chr 1 with average length of each region of 15 million bp?