Interhost variant calling (Data_Tam_DNAseq_2026_19606wt_dAB_dIJ_mito_flu_on_ATCC19606)

  1. Input data:

     mkdir bacto; cd bacto;
     mkdir raw_data; cd raw_data;
    
     # ── Fluoxetine Dataset ──
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcef-1/19606△ABfluEcef-1_1.fq.gz flu_dAB_cef_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcef-1/19606△ABfluEcef-1_2.fq.gz flu_dAB_cef_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcipro-2/19606△ABfluEcipro-2_1.fq.gz flu_dAB_cipro_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcipro-2/19606△ABfluEcipro-2_2.fq.gz flu_dAB_cipro_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEdori-2/19606△ABfluEdori-2_1.fq.gz flu_dAB_dori_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEdori-2/19606△ABfluEdori-2_2.fq.gz flu_dAB_dori_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEnitro-3/19606△ABfluEnitro-3_1.fq.gz flu_dAB_nitro_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEnitro-3/19606△ABfluEnitro-3_2.fq.gz flu_dAB_nitro_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEpip-1/19606△ABfluEpip-1_1.fq.gz flu_dAB_pip_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEpip-1/19606△ABfluEpip-1_2.fq.gz flu_dAB_pip_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEpolyB-3/19606△ABfluEpolyB-3_1.fq.gz flu_dAB_polyB_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEpolyB-3/19606△ABfluEpolyB-3_2.fq.gz flu_dAB_polyB_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEtet-1/19606△ABfluEtet-1_1.fq.gz flu_dAB_tet_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEtet-1/19606△ABfluEtet-1_2.fq.gz flu_dAB_tet_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEcef-4/19606△IJfluEcef-4_1.fq.gz flu_dIJ_cef_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEcef-4/19606△IJfluEcef-4_2.fq.gz flu_dIJ_cef_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEcipro-3/19606△IJfluEcipro-3_1.fq.gz flu_dIJ_cipro_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEcipro-3/19606△IJfluEcipro-3_2.fq.gz flu_dIJ_cipro_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEdori-1/19606△IJfluEdori-1_1.fq.gz flu_dIJ_dori_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEdori-1/19606△IJfluEdori-1_2.fq.gz flu_dIJ_dori_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEnitro-3/19606△IJfluEnitro-3_1.fq.gz flu_dIJ_nitro_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEnitro-3/19606△IJfluEnitro-3_2.fq.gz flu_dIJ_nitro_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEpip-4/19606△IJfluEpip-4_1.fq.gz flu_dIJ_pip_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEpip-4/19606△IJfluEpip-4_2.fq.gz flu_dIJ_pip_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEpolyB-4/19606△IJfluEpolyB-4_1.fq.gz flu_dIJ_polyB_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606△IJfluEpolyB-4/19606△IJfluEpolyB-4_2.fq.gz flu_dIJ_polyB_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEcef-1/19606wtfluEcef-1_1.fq.gz flu_wt_cef_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEcef-1/19606wtfluEcef-1_2.fq.gz flu_wt_cef_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEcipro-2/19606wtfluEcipro-2_1.fq.gz flu_wt_cipro_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEcipro-2/19606wtfluEcipro-2_2.fq.gz flu_wt_cipro_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEdori-1/19606wtfluEdori-1_1.fq.gz flu_wt_dori_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEdori-1/19606wtfluEdori-1_2.fq.gz flu_wt_dori_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEnitro-1/19606wtfluEnitro-1_1.fq.gz flu_wt_nitro_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEnitro-1/19606wtfluEnitro-1_2.fq.gz flu_wt_nitro_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEpip-4/19606wtfluEpip-4_1.fq.gz flu_wt_pip_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEpip-4/19606wtfluEpip-4_2.fq.gz flu_wt_pip_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEpolyB-4/19606wtfluEpolyB-4_1.fq.gz flu_wt_polyB_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEpolyB-4/19606wtfluEpolyB-4_2.fq.gz flu_wt_polyB_R2.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEtet-2/19606wtfluEtet-2_1.fq.gz flu_wt_tet_R1.fastq.gz
     ln -s ../../X101SC25116512-Z01-J003/01.RawData/19606wtfluEtet-2/19606wtfluEtet-2_2.fq.gz flu_wt_tet_R2.fastq.gz
    
     # ── Mitomycin C Dataset ──
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_cipro_1/MitoC_E_AB_cipro_1_1.fq.gz mito_dAB_cipro_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_cipro_1/MitoC_E_AB_cipro_1_2.fq.gz mito_dAB_cipro_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_dori_1/MitoC_E_AB_dori_1_1.fq.gz mito_dAB_dori_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_dori_1/MitoC_E_AB_dori_1_2.fq.gz mito_dAB_dori_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_nitro_2/MitoC_E_AB_nitro_2_1.fq.gz mito_dAB_nitro_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_nitro_2/MitoC_E_AB_nitro_2_2.fq.gz mito_dAB_nitro_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_tet_2/MitoC_E_AB_tet_2_1.fq.gz mito_dAB_tet_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_tet_2/MitoC_E_AB_tet_2_2.fq.gz mito_dAB_tet_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_trime_4/MitoC_E_AB_trime_4_1.fq.gz mito_dAB_trime_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_AB_trime_4/MitoC_E_AB_trime_4_2.fq.gz mito_dAB_trime_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_cipro_1/MitoC_E_IJ_cipro_1_1.fq.gz mito_dIJ_cipro_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_cipro_1/MitoC_E_IJ_cipro_1_2.fq.gz mito_dIJ_cipro_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_dori_4/MitoC_E_IJ_dori_4_1.fq.gz mito_dIJ_dori_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_dori_4/MitoC_E_IJ_dori_4_2.fq.gz mito_dIJ_dori_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_nitro_2/MitoC_E_IJ_nitro_2_1.fq.gz mito_dIJ_nitro_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_nitro_2/MitoC_E_IJ_nitro_2_2.fq.gz mito_dIJ_nitro_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_polyB_3/MitoC_E_IJ_polyB_3_1.fq.gz mito_dIJ_polyB_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_polyB_3/MitoC_E_IJ_polyB_3_2.fq.gz mito_dIJ_polyB_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_tet_3/MitoC_E_IJ_tet_3_1.fq.gz mito_dIJ_tet_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_tet_3/MitoC_E_IJ_tet_3_2.fq.gz mito_dIJ_tet_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_trime_1/MitoC_E_IJ_trime_1_1.fq.gz mito_dIJ_trime_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_IJ_trime_1/MitoC_E_IJ_trime_1_2.fq.gz mito_dIJ_trime_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_cipro_1/MitoC_E_wt_cipro_1_1.fq.gz mito_wt_cipro_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_cipro_1/MitoC_E_wt_cipro_1_2.fq.gz mito_wt_cipro_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_nitro_1/MitoC_E_wt_nitro_1_1.fq.gz mito_wt_nitro_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_nitro_1/MitoC_E_wt_nitro_1_2.fq.gz mito_wt_nitro_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_polyB_1/MitoC_E_wt_polyB_1_1.fq.gz mito_wt_polyB_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_polyB_1/MitoC_E_wt_polyB_1_2.fq.gz mito_wt_polyB_R2.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_trime_2/MitoC_E_wt_trime_2_1.fq.gz mito_wt_trime_R1.fastq.gz
     ln -s ../../X101SC26025981-Z02-J002/01.RawData/MitoC_E_wt_trime_2/MitoC_E_wt_trime_2_2.fq.gz mito_wt_trime_R2.fastq.gz
  2. Call variant calling using snippy

     ln -s ~/Tools/bacto/db/ .;
     ln -s ~/Tools/bacto/envs/ .;
     ln -s ~/Tools/bacto/local/ .;
     cp ~/Tools/bacto/Snakefile .;
     cp ~/Tools/bacto/bacto-0.1.json .;
     cp ~/Tools/bacto/cluster.json .;
    
     #download CP059040.gb from GenBank
     #mv ~/Downloads/sequence\(2\).gb db/CP059040.gb
    
     mamba activate /home/jhuang/miniconda3/envs/bengal3_ac3
     (bengal3_ac3) jhuang@WS-2290C:~/DATA/Data_Tam_DNAseq_2023_A6WT_A10CraA_A12AYE_A1917978$ which snakemake
     /home/jhuang/miniconda3/envs/bengal3_ac3/bin/snakemake
     (bengal3_ac3) jhuang@WS-2290C:~/DATA/Data_Tam_DNAseq_2023_A6WT_A10CraA_A12AYE_A1917978$ snakemake -v
     4.0.0 --> CORRECT!
    
     #NOTE_1: modify bacto-0.1.json keeping only steps assembly, typing_mlst, possibly pangenome and variants_calling true; setting cpu=20 in all used steps.
         #setting the following in bacto-0.1.json
         "fastqc": false,
         "taxonomic_classifier": false,
         "assembly": true,
         "typing_ariba": false,
         "typing_mlst": true,
         "pangenome": true,
         "variants_calling": true,
         "phylogeny_fasttree": false,
         "phylogeny_raxml": false,
         "recombination": false, (due to gubbins-error set false)
    
         "prokka": {
           "genus": "Acinetobacter",
           "kingdom": "Bacteria",
           "species": "baumannii",
           "cpu": 10,
           "evalue": "1e-06",
           "other": ""
         },
    
         "mykrobe": {
           "species": "abaum"
         },
    
         "reference": "db/CP059040.gb"
    
     #NOTE_2: needs disk Titisee since the pipeline needs /media/jhuang/Titisee/GAMOLA2/TIGRfam_db/TIGRFAMs_15.0_HMM.LIB
     snakemake --printshellcmds
  3. Checking the contaminated samples based on the size of genome

     find . -maxdepth 2 -name "contigs.fa" -exec du -h {} \;
     find . -maxdepth 2 -name "contigs.fa" -printf "%s\t%p\n" | sort -nr | \
             while IFS=$'\t' read -r bytes path; do
             sample=$(basename "$(dirname "$path")")
             printf "%-20s %8s\t%s\n" "$sample" "$(numfmt --to=iec-i --suffix=B "$bytes")" "$path"
     done
    
     mito_wt_polyB          8,6MiB   ./mito_wt_polyB/contigs.fa
     mito_wt_trime          8,2MiB   ./mito_wt_trime/contigs.fa
     mito_dAB_trime         8,2MiB   ./mito_dAB_trime/contigs.fa
     flu_wt_cipro           6,7MiB   ./flu_wt_cipro/contigs.fa
     mito_dIJ_nitro         6,6MiB   ./mito_dIJ_nitro/contigs.fa
     flu_dAB_cipro          4,7MiB   ./flu_dAB_cipro/contigs.fa
    
     flu_wt_nitro           3,9MiB   ./flu_wt_nitro/contigs.fa
     flu_wt_polyB           3,9MiB   ./flu_wt_polyB/contigs.fa
     flu_wt_cef             3,9MiB   ./flu_wt_cef/contigs.fa
     flu_wt_dori            3,8MiB   ./flu_wt_dori/contigs.fa
     flu_dIJ_pip            3,8MiB   ./flu_dIJ_pip/contigs.fa
     flu_dIJ_dori           3,8MiB   ./flu_dIJ_dori/contigs.fa
     flu_wt_pip             3,8MiB   ./flu_wt_pip/contigs.fa
     flu_dAB_dori           3,8MiB   ./flu_dAB_dori/contigs.fa
     flu_dIJ_cipro          3,8MiB   ./flu_dIJ_cipro/contigs.fa
     flu_dAB_nitro          3,8MiB   ./flu_dAB_nitro/contigs.fa
     flu_dAB_pip            3,8MiB   ./flu_dAB_pip/contigs.fa
     flu_dAB_polyB          3,8MiB   ./flu_dAB_polyB/contigs.fa
     flu_dIJ_nitro          3,8MiB   ./flu_dIJ_nitro/contigs.fa
     flu_dIJ_cef            3,8MiB   ./flu_dIJ_cef/contigs.fa
     flu_dAB_tet            3,8MiB   ./flu_dAB_tet/contigs.fa
     flu_dIJ_polyB          3,8MiB   ./flu_dIJ_polyB/contigs.fa
     flu_dAB_cef            3,8MiB   ./flu_dAB_cef/contigs.fa
     mito_dIJ_polyB         3,8MiB   ./mito_dIJ_polyB/contigs.fa
     mito_dIJ_cipro         3,8MiB   ./mito_dIJ_cipro/contigs.fa
     mito_dIJ_dori          3,8MiB   ./mito_dIJ_dori/contigs.fa
     flu_wt_tet             3,8MiB   ./flu_wt_tet/contigs.fa
     mito_wt_nitro          3,8MiB   ./mito_wt_nitro/contigs.fa
     mito_wt_cipro          3,8MiB   ./mito_wt_cipro/contigs.fa
     mito_dIJ_tet           3,8MiB   ./mito_dIJ_tet/contigs.fa
     mito_dIJ_trime         3,8MiB   ./mito_dIJ_trime/contigs.fa
     mito_dAB_dori          3,8MiB   ./mito_dAB_dori/contigs.fa
     mito_dAB_cipro         3,7MiB   ./mito_dAB_cipro/contigs.fa
     mito_dAB_tet           3,7MiB   ./mito_dAB_tet/contigs.fa
     mito_dAB_nitro         3,7MiB   ./mito_dAB_nitro/contigs.fa
  4. Summarize all SNPs and Indels from the snippy result directory.

     cp ~/Scripts/summarize_snippy_res_ordered.py .
     # IMPORTANT_ADAPT the array in script should be adapted; deleting the isolates "mito_wt_polyB","mito_wt_trime", "mito_dAB_trime", "flu_wt_cipro", "mito_dIJ_nitro", and "flu_dAB_cipro"
     isolates = ["flu_wt_cef", "flu_wt_dori", "flu_wt_nitro", "flu_wt_pip", "flu_wt_polyB", "flu_wt_tet",    "flu_dAB_cef", "flu_dAB_dori", "flu_dAB_nitro", "flu_dAB_pip", "flu_dAB_polyB", "flu_dAB_tet",    "flu_dIJ_cef", "flu_dIJ_cipro", "flu_dIJ_dori", "flu_dIJ_nitro", "flu_dIJ_pip", "flu_dIJ_polyB",         "mito_dIJ_trime",    "mito_wt_cipro", "mito_wt_nitro",   "mito_dAB_cipro", "mito_dAB_dori", "mito_dAB_nitro", "mito_dAB_tet",     "mito_dIJ_cipro", "mito_dIJ_dori",  "mito_dIJ_polyB", "mito_dIJ_tet"]
    
     mamba activate plot-numpy1
     python3 ./summarize_snippy_res_ordered.py snippy
     #--> Summary CSV file created successfully at: snippy/summary_snps_indels.csv
     cd snippy
     #REMOVE_the_line? I don't find the sence of the line:    grep -v "None,,,,,,None,None" summary_snps_indels.csv > summary_snps_indels_.csv
  5. Using spandx calling variants (almost the same results to the one from viral-ngs!)

     mamba deactivate
     mamba activate /home/jhuang/miniconda3/envs/spandx
    
     # PREPARE the inputs for the options ref and database (NOT ALWAYS NEED, PREPARE ONlY ONCE)
     mkdir ~/miniconda3/envs/spandx/share/snpeff-5.1-2/data/PP810610
     cp PP810610.gb  ~/miniconda3/envs/spandx/share/snpeff-5.1-2/data/PP810610/genes.gbk
     vim ~/miniconda3/envs/spandx/share/snpeff-5.1-2/snpEff.config
     /home/jhuang/miniconda3/envs/spandx/bin/snpEff build PP810610    #-d
     ~/Scripts/genbank2fasta.py PP810610.gb
     mv PP810610.gb_converted.fna PP810610.fasta    #rename "NC_001348.1 xxxxx" to "NC_001348" in the fasta-file
    
     ln -s /home/jhuang/Tools/spandx/ spandx
     # Deleting the contaminated samples flu_wt_cipro*.fastq and flu_dAB_cipro*.fastq
     (spandx) nextflow run spandx/main.nf --fastq "trimmed/*_P_{1,2}.fastq" --ref CP059040.fasta --annotation --database CP059040 -resume
    
     # RERUN SNP_matrix.sh due to the error ERROR_CHROMOSOME_NOT_FOUND in the variants annotation, resulting in all impacts are MODIFIER --> IT WORKS!
     cd Outputs/Master_vcf
     conda activate /home/jhuang/miniconda3/envs/spandx
     (spandx) cp -r ../../snippy/flu_wt_cef/reference . # Eigentlich irgendein directory, all directories contains the same reference.
     (spandx) cp ../../spandx/bin/SNP_matrix.sh ./
     #Note that ${variant_genome_path}=CP059040 in the following command, but it was not used after the following command modification.
     #Adapt "snpEff eff -no-downstream -no-intergenic -ud 100 -formatEff -v ${variant_genome_path} out.vcf > out.annotated.vcf" to
     "/home/jhuang/miniconda3/envs/bengal3_ac3/bin/snpEff eff -no-downstream -no-intergenic -ud 100 -formatEff -c reference/snpeff.config -dataDir . ref out.vcf > out.annotated.vcf" in SNP_matrix.sh
     (spandx) bash SNP_matrix.sh CP059040 .

Cross-Caller SNP/Indel Concordance & Invariant Variant Analyzer; Multi-Isolate Variant Intersection, Annotation Harmonization & Caller Discrepancy Report; Comparative Genomic Variant Profiling: Concordance, Invariance & Allele Mismatch Analysis; VarMatch: Cross-Tool Variant Concordance Pipeline

  1. Calling inter-host variants by merging the results from snippy+spandx

     mamba activate plot-numpy1
     cd bacto
     cp Outputs/Master_vcf/All_SNPs_indels_annotated.txt .
     cp snippy/summary_snps_indels.csv .
    
     cp ~/Scripts/process_variants_snippy_alleles_spandx_annotations.py .
    
     #Configuring
     #Delete "mito_wt_polyB", "mito_wt_trime", "mito_dAB_trime", "flu_wt_cipro", "mito_dIJ_nitro", and "flu_dAB_cipro"
             ISOLATES = [
             "flu_wt_cef", "flu_wt_dori", "flu_wt_nitro", "flu_wt_pip", "flu_wt_polyB", "flu_wt_tet",
             "flu_dAB_cef", "flu_dAB_dori", "flu_dAB_nitro", "flu_dAB_pip", "flu_dAB_polyB", "flu_dAB_tet",
             "flu_dIJ_cef", "flu_dIJ_cipro", "flu_dIJ_dori", "flu_dIJ_nitro", "flu_dIJ_pip", "flu_dIJ_polyB",
             "mito_dIJ_trime",
             "mito_wt_cipro", "mito_wt_nitro",
             "mito_dAB_cipro", "mito_dAB_dori", "mito_dAB_nitro", "mito_dAB_tet",
             "mito_dIJ_cipro", "mito_dIJ_dori", "mito_dIJ_polyB", "mito_dIJ_tet"
             ]
    
     (plot-numpy1) python process_variants_snippy_alleles_spandx_annotations.py
    
     # -- Indeed, the generated files are the common SNPs generated by snippy+spandx, therefore, we need to modify the filenames. --
     mv common_variants_all_snippy_annotated.csv common_variants_snippy+spandx_annotated.csv
     mv common_variants_invariant_snippy_annotated.csv common_invariants_snippy+spandx_annotated.csv
     mv common_variants_all_snippy_annotated.xlsx common_variants_snippy+spandx_annotated.xlsx
     mv common_variants_invariant_snippy_annotated.xlsx common_invariants_snippy+spandx_annotated.xlsx
  2. Manully checking each of the 6 records by comparing them to the results from SPANDx; three are confirmed!

     #The file will only contain rows where at least one of the 29 samples had a different allele between the two files. You can open allele_differences.xlsx side-by-side with your original common_variants_all_snippy_annotated.xlsx for fast, column-aligned manual verification.
     mamba activate plot-numpy1
     (plot-numpy1) python ~/Scripts/export_mismatch_alleles.py common_variants_snippy+spandx_annotated.csv All_SNPs_indels_annotated.txt
     #❌ Found 13 mismatched positions. Extracting & formatting...
    
     # The export_mismatch_alleles.py always generated the same output-file, avoid to recoved by the following commands, modify the generated filename.
     (plot-numpy1) mv allele_differences.xlsx allele_differences_for_cmp.xlsx
    
     (plot-numpy1) python ~/Scripts/export_mismatch_alleles.py common_invariants_snippy+spandx_annotated.csv All_SNPs_indels_annotated.txt
     #✅ All alleles match perfectly across all common positions and samples!
    
     cp common_variants_all_snippy_annotated.xlsx common_variants_all_snippy_annotated_for_cmp.xlsx
     #Then marked the corresponding rows in yellow, then compare it to allele_differences.xlsx.
    
     # IMPORTANT_MANUAL_CHECK: checking all variants of common_variants_snippy+spandx_annotated.xlsx and common_invariants_snippy+spandx_annotated.xlsx by comparing allele_differences_for_cmp.xlsx.
  3. Run nextflow bacass

     # Download the kmerfinder database: https://www.genomicepidemiology.org/services/ --> https://cge.food.dtu.dk/services/KmerFinder/ --> https://cge.food.dtu.dk/services/KmerFinder/etc/kmerfinder_db.tar.gz
     # Download 20190108_kmerfinder_stable_dirs.tar.gz from https://zenodo.org/records/13447056
     #--kmerfinderdb /mnt/nvme1n1p1/REFs/kmerfinder_db.tar.gz
     #--kmerfinderdb /mnt/nvme1n1p1/REFs/20190108_kmerfinder_stable_dirs.tar.gz
     nextflow run nf-core/bacass -r 2.5.0 -profile docker \
     --input samplesheet.tsv \
     --outdir bacass_out \
     --assembly_type short \
     --kraken2db /mnt/nvme1n1p1/REFs/k2_standard_08_GB_20251015.tar.gz \
     --kmerfinderdb /mnt/nvme1n1p1/REFs/kmerfinder/bacteria/ \
     -resume
     #Possibly the chraracter '△' is a problem.
     #Solution: 19606△ABfluEcef-1 → 19606delABfluEcef-1
    
     #SAVE bacass_out/Kmerfinder/kmerfinder_summary.csv to bacass_out/Kmerfinder/An6?/An6?_kmerfinder_results.xlsx
    
     samplesheet.tsv
     sample,fastq_1,fastq_2
     flu_dAB_cef,../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcef-1/19606△ABfluEcef-1_1.fq.gz,../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcef-1/19606△ABfluEcef-1_2.fq.gz
     flu_dAB_cipro,../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcipro-2/19606△ABfluEcipro-2_1.fq.gz,../X101SC25116512-Z01-J003/01.RawData/19606△ABfluEcipro-2/19606△ABfluEcipro-2_2.fq.gz
    
     #busco example results:
     Input_file      Dataset Complete        Single  Duplicated      Fragmented      Missing n_markers       Scaffold N50    Contigs N50     Percent gaps    Number of scaffolds
     wt_cef.scaffolds.fa     bacteria_odb10  98.4    98.4    0.0     1.6     0.0     124     285852  285852  0.000%  45
     wt_cipro.scaffolds.fa   bacteria_odb10  90.3    89.5    0.8     8.1     1.6     124     7434    7434    0.000%  1699
  4. Run bactmap

     nextflow run nf-core/bactmap -r 1.0.0 -profile docker \
     --input samplesheet.csv \
     --reference CP059040.fasta \
     --outdir bactmap_out \
     -resume
    
     nextflow run nf-core/bactmap -r 1.0.0 -profile docker \
     --input samplesheet.csv \
     --reference CU459141.fasta \
     --outdir bactmap_out \
     -resume
    
     sample,fastq_1,fastq_2
     G18582004,fastqs/G18582004_1.fastq.gz,fastqs/G18582004_2.fastq.gz
     G18756254,fastqs/G18756254_1.fastq.gz,fastqs/G18756254_2.fastq.gz
     G18582006,fastqs/G18582006_1.fastq.gz,fastqs/G18582006_2.fastq.gz
    
     mkdir bactmap_workspace
     #Prepare reference.fasta (example for CP059040.fasta) in bactmap_workspace and samplesheet.csv in bactmap_workspace
     nextflow run nf-core/bactmap -r 1.0.0 -profile docker \
     --input samplesheet.csv \
     --reference CP059040.fasta \
     --outdir bactmap_out \
     -resume
  5. Structural variant calling

     conda activate sv_assembly
    
     nucmer --maxmatch -l 100 -c 500 bacto/CP059040.fasta bacto/shovill/flu_wt_cef/contigs.fa -p flu_wt_cef
     delta-filter -1 -q flu_wt_cef.delta > flu_wt_cef.filtered.delta
     Assemblytics flu_wt_cef.filtered.delta flu_wt_cef_assemblytics 1000 100 50000
    
     #reference  ref_start  ref_stop  ID                size  strand  type                ref_gap_size  query_gap_size  query_coordinates          method
     CP059040    3124916    3125037   Assemblytics_b_3  198   +       Tandem_contraction  121           -77             contig00010:34383-34460:-  between_alignments
    
     for sample in flu_wt_cef  flu_wt_dori  flu_wt_nitro  flu_wt_pip  flu_wt_polyB  flu_wt_tet  flu_dAB_cef  flu_dAB_dori  flu_dAB_nitro  flu_dAB_pip  flu_dAB_polyB  flu_dAB_tet  flu_dIJ_cef  flu_dIJ_cipro  flu_dIJ_dori  flu_dIJ_nitro  flu_dIJ_pip  flu_dIJ_polyB  mito_dIJ_trime  mito_wt_cipro  mito_wt_nitro  mito_dAB_cipro  mito_dAB_dori  mito_dAB_nitro  mito_dAB_tet  mito_dIJ_cipro  mito_dIJ_dori  mito_dIJ_polyB  mito_dIJ_tet; do
             nucmer --maxmatch -l 100 -c 500 bacto/CP059040.fasta bacto/shovill/${sample}/contigs.fa -p ${sample};
             delta-filter -1 -q ${sample}.delta > ${sample}.filtered.delta;
             Assemblytics ${sample}.filtered.delta ${sample}_assemblytics 1000 100 50000;
     done
    
     #NOTE that We excluded 6 samples with abnormal assembly sizes (>4.5 Mb or <3.7 Mb), which likely reflect contamination or fragmentation. The final merged SV table (merged_sv_results_filtered.tsv) contains 29 high-quality isolates and is ready for downstream analysis.
     #mito_wt_polyB          8,6MiB   ./mito_wt_polyB/contigs.fa
     #mito_wt_trime          8,2MiB   ./mito_wt_trime/contigs.fa
     #mito_dAB_trime         8,2MiB   ./mito_dAB_trime/contigs.fa
     #flu_wt_cipro           6,7MiB   ./flu_wt_cipro/contigs.fa
     #mito_dIJ_nitro         6,6MiB   ./mito_dIJ_nitro/contigs.fa
     #flu_dAB_cipro          4,7MiB   ./flu_dAB_cipro/contigs.fa
    
     mito_wt_polyB
     # Adapt the EXCLUDE_SAMPLES names in the following script and run it.
     merge_sv_filtered.sh  # merged_sv_results.txt
     #✅ Merge complete: merged_sv_results_filtered.txt
     #• Included: 29 samples
     #• Excluded: 4 samples (Indeed, 6 samples should not include in the calculation, but 2 samples was not run in the last step.)

Leave a Reply

Your email address will not be published. Required fields are marked *