DME: The Drug Metabolising Enzyme software

Introduction

The microbiome can break down or modify xenobiotics (i.e., externally administered drugs), regulate host gene expression, and modulate xenobiotic absorption. The drug metabolism is not limited to orally administered drugs, the microbiome also converts drug metabolites destined for excretion via the gut, including drug conjugates from the liver

This application is to predict drug-metabolizing enzymes from protein or nucleotide data based on homology models. The application uses reference data from the Human Microbiome Drug Metabolism (HMDM) Database.

Overview of DME

If DNA sequences are submitted, DME first predicts complete open reading frames (ORFs) using Prodigal (ignoring those less than 30 bp) and analyzes the predicted protein sequences. This includes a secondary correction by DME if Prodigal undercalls the correct start codon to ensure complete genes are predicted. However, if Prodigal fails to predict an ORF for a gene, this will produce a false negative result.

If protein sequences are submitted, DME skips ORF prediction and uses the protein sequences directly.

The DME currently supports HMDM's protein homolog models (use of BLASTP or DIAMOND bitscore cut-offs to detect functional homologs of enzymes).

Example	Enzyme
Protein Homolog Model	TDC

The DME analyzes genome or proteome sequences under three paradigms: Perfect, Strict, and Loose (a.k.a. Discovery).

Installation

The tool requires Python >= 3.11 and conda >= 4.12.0. The latest release can be installed directly from pip or this repository.

pip install dme

or

python3 -m pip install /path/to/dme-1.0.0.tar.gz

Dependencies

• Python 3.6
• NCBI BLAST 2.9.0
• zlib
• Prodigal 2.6.3
• DIAMOND 0.8.36
• Biopython 1.78
• filetype 1.0.0+
• pytest 3.0.0+
• pandas 0.15.0+
• Matplotlib 2.1.2+
• seaborn 0.8.1+
• pyfaidx 0.5.4.1+
• pyahocorasick 1.1.7+
• OligoArrayAux 3.8
• samtools 1.9
• bamtools 2.5.1
• bedtools 2.27.1
• Jellyfish 2.2.10
• Bowtie2 2.3.4.3
• BWA 0.7.17 (r1188)
• KMA 1.3.4

DME Usage

usage: dme <command> [<args>]
            commands are:
               ---------------------------------------------------------------------------------------
               Database
               ---------------------------------------------------------------------------------------
               auto_load Automatically loads HMDM database, annotations and k-mer database
               load      Loads HMDM database, annotations and k-mer database
               clean     Removes BLAST databases and temporary files
               database  Information on installed hmdm database

               ---------------------------------------------------------------------------------------
               Genomic
               ---------------------------------------------------------------------------------------

               main     Runs dme application
               tab      Creates a Tab-delimited from dme results

               

Drug Metabolising Enzyme (DME) - 1.0.0

positional arguments:
  {main,tab,load,auto_load,clean,database}
                        Subcommand to run

options:
  -h, --help            show this help message and exit

Use the Drug Metabolising Enzyme (DME) to predict drug-metabolizing enzymes from protein or nucleotide data based on homology models. Check https://hmdm.mcmaster.ca/download for software and data updates.
Receive email notification of monthly HMDM updates via the HMDM Mailing List (https://mailman.mcmaster.ca/mailman/listinfo/hmdm-l)