gnomonicus

gnomonicus

Python code to integrate results of tb-pipeline and provide an antibiogram, mutations and variations

Provides a library of functions for use within scripts, as well as a CLI tool for linking the functions together to produce output

Documentation

API reference for developers, and CLI instructions can be found here: https://oxfordmmm.github.io/gnomonicus/

Usage

usage: gnomonicus [-h] [-v] --vcf_file VCF_FILE --genome_object GENOME_OBJECT [--catalogue_file CATALOGUE_FILE] [--ignore_vcf_filter] [--output_dir OUTPUT_DIR] [--json] [--csvs CSVS [CSVS ...]] [--debug]
                  [--resistance_genes] --min_dp MIN_DP

options:
  -h, --help            show this help message and exit
  -v, --version         show program's version number and exit
  --vcf_file VCF_FILE   the path to a single VCF file
  --genome_object GENOME_OBJECT
                        the path to a genbank file
  --catalogue_file CATALOGUE_FILE
                        the path to the resistance catalogue
  --ignore_vcf_filter   whether to ignore the FILTER field in the vcf (e.g. necessary for some versions of Clockwork VCFs)
  --output_dir OUTPUT_DIR
                        Directory to save output files to. Defaults to wherever the script is run from.
  --json                Flag to create a single JSON output as well as the CSVs
  --csvs CSVS [CSVS ...]
                        Types of CSV to produce. Accepted values are [variants, mutations, effects, predictions, all]. `all` produces all of the CSVs
  --debug               Whether to log debugging messages to the log. Defaults to False
  --resistance_genes    Flag to filter mutations and variants to only include genes present in the resistance catalogue
  --min_dp MIN_DP       Minimum depth for a variant to be considered in the VCF. Below this value, rows are interpreted as null calls.

Install

Simple install using pip for the latest release

pip install gnomonicus

Install from source

git clone https://github.com/oxfordmmm/gnomonicus.git
cd gnomonicus
pip install -e .

Docker

A Docker image should be built on releases. To open a shell with gnomonicus installed:

docker run -it oxfordmmm/gnomonicus:latest

Notes

When generating mutations, in cases of synonymous amino acid mutation, the nucelotides changed are also included. This can lead to a mix of nucleotides and amino acids for coding genes, but these are excluded from generating effects unless specified in the catalogue. This means that the default rule of gene@*= --> S is still in place regardless of the introduced gene@*? which would otherwise take precedence. For example:

  'MUTATIONS': [
      {
          'MUTATION': 'F2F',
          'GENE': 'S',
          'GENE_POSITION': 2
      },
      {
          'MUTATION': 't6c',
          'GENE': 'S',
          'GENE_POSITION': 6
      },
  ],
  'EFFECTS': {
      'AAA': [
          {
              'GENE': 'S',
              'MUTATION': 'F2F',
              'PREDICTION': 'S'
          },
          {
              'PHENOTYPE': 'S'
          }
      ],
  }

The nucelotide variation is included in the the MUTATIONS, but explictly removed from the EFFECTS unless it is specified within the catalogue. In order for this variation to be included, a line in the catalogue of S@F2F&S@t6c would have to be present.

User stories

1. As a bioinformatician, I want to be able to run gnomonicus on the command line, passing it (i) a GenBank file (or pickled gumpy.Genome object), (ii) a resistance catalogue and (iii) a VCF file, and get back pandas.DataFrames of the genetic variants, mutations, effects and predictions/antibiogram. The latter is for all the drugs described in the passed resistance catalogue.

2. As a GPAS developer, I want to be able to embed gnomonicus in a Docker image/NextFlow pipeline that consumes the outputs of tb-pipeline and emits a structured, well-designed JSON object describing the genetic variants, mutations, effects and predictions/antibiogram.

3. In general, I would also like the option to output fixed- and variable-length FASTA files (the latter takes into account insertions and deletions described in any input VCF file).

Unit testing

For speed, rather than use NC_000962.3 (i.e. H37Rv M. tuberculosis), we shall use SARS-CoV-2 and have created a fictious drug resistance catalogue, along with some vcf files and the expected outputs in tests/.

These can be run with pytest -vv