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Dr PRG

Dr. PRG - Drug resistance Prediction with Reference Graphs️

About : |

As the name suggests, Dr. PRG (pronounced "Doctor P-R-G") is a tool for predicting drug resistance from sequencing data.

Grandeur only uses Dr. PRG for TB antibiotic susceptible/resistant profiles.

Documentation : https://github.com/mbhall88/drprg

Citation : https://www.microbiologyresearch.org/content/journal/mgen/10.1099/mgen.0.001081

Directory tree:

drprg/
├── drprg_summary.tsv
├── sample
│   ├── discover
│   │   ├── denovo_paths.txt
│   │   ├── denovo_sequences.fa
│   │   ├── discover.log
│   │   └── sample
│   │       ├── denovo_paths.txt
│   │       ├── denovo_sequences.fa
│   │       ├── sample.filtered.sam
│   │       ├── pandora.consensus.fq.gz
│   │       └── pandora.pangraph.gfa
│   ├── kmer_covgs.txt
│   ├── kmer_probs.txt
│   ├── sample.drprg.bcf
│   ├── sample.drprg.json
│   ├── sample.filtered.sam
│   ├── pandora.consensus.fq.gz
│   ├── pandora_consensus.vcf
│   ├── pandora_genotyped.vcf
│   ├── pandora.log
│   └── pandora.pangraph.gfa
└── sample_drprg.tsv

Example file for an individual sample (sample.drprg.json)

{
  "genes": {
    "absent": [],
    "present": [
      "ahpC",
      "ddn",
      "eis",
      "embA",
      "embB",
      "ethA",
      "fabG1",
      "gid",
      "gyrA",
      "gyrB",
      "inhA",
      "katG",
      "pncA",
      "rplC",
      "rpoB",
      "rpsL",
      "rrs",
      "tlyA"
    ]
  },
  "sample": "myco_GCF_000195955.2",
  "susceptibility": {
    "Amikacin": {
      "evidence": [
        {
          "gene": "eis",
          "residue": "DNA",
          "variant": "C-14T",
          "vcfid": "e64f7e27"
        },
        {
          "gene": "rrs",
          "residue": "DNA",
          "variant": "G1484X",
          "vcfid": "9049e055"
        }
      ],
      "predict": "F"
    },
    "Capreomycin": {
      "evidence": [
        {
          "gene": "rrs",
          "residue": "DNA",
          "variant": "G1484X",
          "vcfid": "9049e055"
        }
      ],
      "predict": "F"
    },
    "Ciprofloxacin": {
      "evidence": [
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88A",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88C",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "S91P",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "A90V",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94N",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94Y",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94G",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94H",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94A",
          "vcfid": "9dbd1282"
        }
      ],
      "predict": "F"
    },
    "Delamanid": {
      "evidence": [],
      "predict": "S"
    },
    "Ethambutol": {
      "evidence": [
        {
          "gene": "embA",
          "residue": "DNA",
          "variant": "C-16T",
          "vcfid": "d2217772"
        },
        {
          "gene": "embA",
          "residue": "DNA",
          "variant": "C-16G",
          "vcfid": "d2217772"
        },
        {
          "gene": "embA",
          "residue": "DNA",
          "variant": "C-12T",
          "vcfid": "d2217772"
        }
      ],
      "predict": "F"
    },
    "Ethionamide": {
      "evidence": [],
      "predict": "S"
    },
    "Isoniazid": {
      "evidence": [
        {
          "gene": "ahpC",
          "residue": "DNA",
          "variant": "C-72T",
          "vcfid": "c3e661f6"
        },
        {
          "gene": "inhA",
          "residue": "PROT",
          "variant": "I194T",
          "vcfid": "5330b912"
        }
      ],
      "predict": "F"
    },
    "Kanamycin": {
      "evidence": [
        {
          "gene": "eis",
          "residue": "DNA",
          "variant": "C-12T",
          "vcfid": "e64f7e27"
        },
        {
          "gene": "eis",
          "residue": "DNA",
          "variant": "G-10A",
          "vcfid": "e64f7e27"
        },
        {
          "gene": "eis",
          "residue": "DNA",
          "variant": "C-14T",
          "vcfid": "e64f7e27"
        },
        {
          "gene": "rrs",
          "residue": "DNA",
          "variant": "G1484X",
          "vcfid": "9049e055"
        }
      ],
      "predict": "F"
    },
    "Levofloxacin": {
      "evidence": [
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88A",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88C",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "S91P",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "A90V",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94N",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94Y",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94G",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94H",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94A",
          "vcfid": "9dbd1282"
        }
      ],
      "predict": "F"
    },
    "Linezolid": {
      "evidence": [
        {
          "gene": "rplC",
          "residue": "PROT",
          "variant": "C154R",
          "vcfid": "ac3cfc1b"
        }
      ],
      "predict": "F"
    },
    "Moxifloxacin": {
      "evidence": [
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88A",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88C",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "S91P",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "A90V",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94N",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94Y",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94G",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94H",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94A",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94C",
          "vcfid": "9dbd1282"
        }
      ],
      "predict": "F"
    },
    "Ofloxacin": {
      "evidence": [
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88A",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88C",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "G88N",
          "vcfid": "e1c2ee47"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "S91P",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "A90V",
          "vcfid": "50c740bf"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94N",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94Y",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94G",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94H",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94A",
          "vcfid": "9dbd1282"
        },
        {
          "gene": "gyrA",
          "residue": "PROT",
          "variant": "D94C",
          "vcfid": "9dbd1282"
        }
      ],
      "predict": "F"
    },
    "Pyrazinamide": {
      "evidence": [
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "D49Y",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "D49H",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "D49E",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H51L",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H51Y",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H51N",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H51P",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "D49A",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H51R",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H51D",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "D49G",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TTC148TTT",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H51Q",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "D49N",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "D49V",
          "vcfid": "0a83770f"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H57Q",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H57L",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "F58I",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H57Y",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CGGGTGACCA161A",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H57N",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H57D",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "F58S",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H57R",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "F58L",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "H57P",
          "vcfid": "541508c6"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P62R",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CCG184CCC",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P62S",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P62T",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P62Q",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P62L",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "C185CGGACTATTC",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P62A",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CCG184CCA",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CGGCACACCGGACTATTCCTCGTCG177ACCGGACTATTCCTCGTCG",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CCG184CCT",
          "vcfid": "54447e1e"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CGGCACACCGGACTATTCCTCGTCG177ACCGGACTATTCCTCGTCG",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P69Q",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "W68G",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "W68L",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TCG199TAA",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "S67P",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TCG199TAG",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TGG202TGA",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "W68R",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "W68C",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "P69L",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TGG202TAA",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "ACTATTCCTCGTCG188AG",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TGG202TAG",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TCG199TGA",
          "vcfid": "19ad43e1"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "T76S",
          "vcfid": "79f0cd6a"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "AGCGGTACTCCCG220G",
          "vcfid": "79f0cd6a"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "T76P",
          "vcfid": "79f0cd6a"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "T76I",
          "vcfid": "79f0cd6a"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TGCGGCAACGCGGCGTCGATGAGGTCGATGTGGTCGGTAT359TGCGGCAACGCGGCGTCGATGAGGTCGGTAT",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "GTC373GTA",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "GTC373GTG",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "V125G",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "TGCGGCAACGCGGCGTCGATGAGGTCGATGTGGTCGGTAT359TGCGGCAACGCGGCGTGGTCGGTAT",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "V125A",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "GTC373GTT",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "V125F",
          "vcfid": "9a1a029b"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CAG421TAG",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "ACG424ACA",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "Q141P",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "ACG424ACC",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "T142R",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CAG421TAA",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "ACG424ACT",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "DNA",
          "variant": "CAG421TGA",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "T142K",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "T142A",
          "vcfid": "2183643d"
        },
        {
          "gene": "pncA",
          "residue": "PROT",
          "variant": "T142M",
          "vcfid": "2183643d"
        }
      ],
      "predict": "F"
    },
    "Rifampicin": {
      "evidence": [
        {
          "gene": "rpoB",
          "residue": "PROT",
          "variant": "V170F",
          "vcfid": "33ebe38d"
        },
        {
          "gene": "rpoB",
          "residue": "DNA",
          "variant": "GACCAGAACAACCCGCTGTCGGGGTTGACCCACA1303GCCCAGAACAACCCGCTGTCCGGGCCCC",
          "vcfid": "4020ad9c"
        },
        {
          "gene": "rpoB",
          "residue": "DNA",
          "variant": "CCCACAAG1331CC",
          "vcfid": "3759d176"
        },
        {
          "gene": "rpoB",
          "residue": "DNA",
          "variant": "TTGACCCACAA1327TGGCCCCA",
          "vcfid": "3759d176"
        },
        {
          "gene": "rpoB",
          "residue": "DNA",
          "variant": "TGACCCACAA1328GGCCCCA",
          "vcfid": "3759d176"
        },
        {
          "gene": "rpoB",
          "residue": "DNA",
          "variant": "GACCAGAACAACCCGCTGTCGGGGTTGACCCACA1303GCCCAGAACAACCCGCTGTCCGGGCCCC",
          "vcfid": "3759d176"
        },
        {
          "gene": "rpoB",
          "residue": "DNA",
          "variant": "ACTGTCGGCG1344A",
          "vcfid": "9fdf7754"
        }
      ],
      "predict": "F"
    },
    "Streptomycin": {
      "evidence": [
        {
          "gene": "gid",
          "residue": "DNA",
          "variant": "ATATCGGTAGCGGAGC200C",
          "vcfid": "290d169a"
        },
        {
          "gene": "gid",
          "residue": "DNA",
          "variant": "ATATCGGTAGCGGAGCC200CC",
          "vcfid": "290d169a"
        }
      ],
      "predict": "F"
    }
  },
  "version": {
    "drprg": "0.1.1",
    "index": "20230308"
  }
}

Example file for run (drprg/drprg_summary.tsv)

sample	genes_present	genes_absent	susceptibility
myco_GCF_000195955.2	ahpC,ddn,eis,embA,embB,ethA,fabG1,gid,gyrA,gyrB,inhA,katG,pncA,rplC,rpoB,rpsL,rrs,tlyA		Amikacin,Capreomycin,Ciprofloxacin,Delamanid,Ethambutol,Ethionamide,Isoniazid,Kanamycin,Levofloxacin,Linezolid,Moxifloxacin,Ofloxacin,Pyrazinamide,Rifampicin,Streptomycin
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