DeNovoGear is az software for analyzing de novo mutations from familial and somatic tissue sequencing data. It uses likelihood-based error modeling to reduce the false positive rate of mutation discovery in exome analysis and fragment information to identify the parental origin of germ-line mutations. DeNovoGear has been used on human whole-genome sequencing data to produce a set of predicted de novo insertion and/or deletion (indel) mutations.

Reference:

• Avinash Ramu, Michiel J Noordam, Rachel S Schwartz, Arthur Wuster, Matthew E Hurles, Reed A Cartwright and Donald F Conrad
  DeNovoGear: de novo indel and point mutation discovery and phasing
  Nature Methods, 2013, 10(10), p.985.
  Documentation
  • DeNovoGear Github page
  Important Notes
  • Module Name: denovogear (see the modules page for more information)
  • Unusual environment variables set
    • DENOVOGEAR_HOME  installation directory
    • DENOVOGEAR_BIN       executable directory
    • DENOVOGEAR_SRC       source code directory
    • DENOVOGEAR_DATA  sample data directory
  Interactive job
  Interactive jobs should be used for debugging, graphics, or applications that cannot be run as batch jobs.

  Allocate an interactive session and run the program. Sample session:

  [user@biowulf]$ sinteractive --mem=12g -c5 --gres=lscratch:10
  [user@cn3335 ~]$ module load denovogear 
  [+] Loading samtools 1.17  ...
  [+] Loading denovogear 1.1.1  ...
  [user@cn3335 ~]$
  [user@cn3335 ~]$ dng
  USAGE: dng command [options]
         dng help
         dng help [command]
  [user@cn3335 ~]$ dng-dnm
  DeNovoGear v1.1.1
  
  Usage:
  Autosomes:
          dng dnm auto --bcf bcf_f --ped ped_f [OR] dng dnm auto --vcf vcf_f --ped ped_f
  X chromosome in male offspring:
          dng dnm XS --bcf bcf_f --ped ped_f [OR] dng dnm XS --vcf vcf_f --ped ped_f
  X chromosome in female offspring:
          dng dnm XD --bcf bcf_f --ped ped_f [OR] dng dnm XD --vcf vcf_f --ped ped_f
  
  Input:
  DNM:
  --ped:   Ped file to describe relationship between the samples.
  --bcf:   BCF file, contains per-sample read depths and genotype likelihoods.
  --vcf:   VCF file, contains per-sample read depths and genotype likelihoods.
  Phaser:
  --dnm: Tab delimited list of denovo mutations to be phased, format: chr pos inherited_base denovo_base.[example: 1 2000 A C]
  --pgt: Tab delimited genotypes of child and parents at SNP sites near denovo sites, format: chr pos GT_child GT_parent1 GT_parent2.[example: 1 2000 AC AC AA]
  --bam: alignment file (.bam) of the child.
  --window: optional argument which is the maximum distance between the DNM and a phasing site. The default value is 1000.
  
  Output:
  --output_vcf:    vcf file to write the output to.
  
  Parameters:
  --snp_mrate:     Mutation rate prior for SNPs. [1e-8]
  --indel_mrate:   Mutation rate prior for INDELs. [1e-9]
  --pair_mrate:    Mutation rate prior for paired sample analysis. [1e-9]
  --indel_mu_scale:        Scaling factor for indel mutation rate. [1]
  --pp_cutoff:     Posterior probability threshold. [0.0001]
  --rd_cutoff:     Read depth filter, sites where either one of the sample have read depth less than this threshold are filtered out. [10]
  --region:        Region of the BCF file to perform denovo calling. [string of the form "chr:start-end"
  [user@cn3335 ~]$ dng-call
  Usage:
    dng call [options] input1 input2 input3 ...
  
  Allowed Options:
    -f [ --fasta ] arg                 faidx indexed reference sequence file
    -l [ --min-qlen ] arg (=0)         minimum query length
    -m [ --min-prob ] arg (=0.1)       minimum probability for reporting a
                                       mutation
    --mu arg (=1e-9)                   the germline mutation rate
    --mu-somatic arg (=0)              the somatic mutation rate
    --mu-library arg (=0)              the library prep mutation rate
    --nuc-freqs arg (=0.3,0.2,0.2,0.3) nucleotide frequencies in ACGT order
    -p [ --ped ] arg                   the pedigree file
    -q [ --min-basequal ] arg (=0)     minimum base quality
    -Q [ --min-mapqual ] arg (=0)      minimum mapping quality
    -r [ --region ] arg                chromosomal region
    -R [ --ref-weight ] arg (=1)       weight given to reference base for
                                       population prior
    -s [ --sam-files ] arg             file containing a list of input filenames,
                                       one per line
    --theta arg (=0.001)               the population diversity
    -o [ --output ] arg (=-)           Output VCF/BCF file
    --version                          display version information
    --help                             display usage informaiton
    --arg-file arg                     read command-line arguments from a file
  [user@cn3335 ~]$ 
  
  

  etc.
  
  End the interactive session:

  [user@cn3335 ~]$ exit
  salloc.exe: Relinquishing job allocation 46116226
  [user@biowulf ~]$