Metabolites prediction for toxicology

Overview

In silico prediction of a list of molecules whose SMILES code is provided by 4 software packages : BioTransformer3, SyGMa, MetaTrans and Meta-Predictor.

Biotransformer and Sygma are used via singularity, Meta-Trans & Meta-Predictor need to clone their github.

As this project was designed for non-bioinformaticians, a graphical interface via zenity was included (optional).

This project has been tested and run on linux and windows (WSL).

Due to hardware limitations, MetaTrans and Meta-Predictor may not function correctly. Their use is therefore disabled by default.

Quick start

Required packages:

• Singularity (https://docs.sylabs.io/guides/3.0/user-guide/installation.html) : sudo apt-get install -y singularity-container

• Conda (https://docs.conda.io/projects/conda/en/latest/user-guide/install/index.html) :

  wget https://repo.anaconda.com/miniconda/Miniconda3-latest-Linux-x86_64.sh; chmod +x Miniconda3-latest-Linux-x86_64.sh; ./Miniconda3-latest-Linux-x86_64.sh

• Necessary for metatrans conda env install : conda config --set channel_priority flexible

• Some packages needed : sudo apt install zenity gawk dos2unix csvkit

Download project, MetaTrans-MetaPredictor directory and configure them:

• git clone https://github.com/alexisbourdais/MetaTox; cd MetaTox/; git clone https://github.com/KavrakiLab/MetaTrans; git clone https://github.com/zhukeyun/Meta-Predictor; mkdir Meta-Predictor/prediction; mv Meta-Predictor/model/SoM\ identifier/ Meta-Predictor/model/SoM_identifier; mv Meta-Predictor/model/metabolite\ predictor/ Meta-Predictor/model/metabolite_predictor; chmod +x Meta-Predictor/predict-top15.sh Metatox.sh
• download the models in https://rice.app.box.com/s/5jeb5pp0a3jjr3jvkakfmck4gi71opo0 and place them in MetaTrans/models/ (unarchived)

Run

• Input : Text file with the molecule ID/name in the 1st column and the smile code in the 2nd column, separated by a comma.
• ./Metatox.sh to activate zenity
• ./Metatox.sh --input input_file to skip zenity

Parameters

• ./Metatox.sh -h to see available parameters when zenity was skipped

  REQUIRED parameter
  
    -i|--input
  
  OPTIONAL parameter
  
    -m|--meta       To activate metaTrans and meta-Predictor [No]
  
    -t|--type       Type of biotransformation to use with BioTransformer3:
                        [allHuman] : Predicts all possible metabolites from any applicable reaction(Oxidation, reduction, (de-)conjugation) at each step 
                        ecbased    : Prediction of promiscuous metabolism (e.g. glycerolipid metabolism). EC-based metabolism is also called Enzyme Commission based metabolism
                        cyp450     : CYP450 metabolism prediction 
                        phaseII    : Prediction of major conjugative reactions, including glucuronidation, sulfation, glycine transfer, N-acetyl transfer, and glutathione transfer, among others 
                        hgut       : Human gut microbial
                        superbio   : Runs a set number of transformation steps in a pre-defined order (e.g. deconjugation first, then Oxidation/reduction, etc.)
                        envimicro  : Environmental microbial
  
    -n|--nstep      The number of steps for the prediction by BioTransformer [default=1]
  
    -c|--cmode      CYP450 prediction Mode uses by BioTransformer: 
                        1  = CypReact+BioTransformer rules
                        2  = CyProduct only
                       [3] = CypReact+BioTransformer rules+CyProducts
                
    -1|--phase1     Number of reaction cycles Phase 1 by SygMa [defaut=1]
    -2|--phase2     Number of reaction cycles Phase 2 by SygMa [defaut=1]
  
    -p|--tmp        To keep intermediate files [No]
  

Documentation

BioTransformer3 : https://bitbucket.org/wishartlab/biotransformer3.0jar/src/master/

SyGMa : https://github.com/3D-e-Chem/sygma

MetaTrans : https://github.com/KavrakiLab/MetaTrans

Meta-Predictor : https://github.com/zhukeyun/Meta-Predictor/tree/main

Citation

BioTransformer : Djoumbou-Feunang, Y. et al. BioTransformer: a comprehensive computational tool for small molecule metabolism prediction and metabolite identification. J Cheminform 11, 2 (2019)

SyGMa : Ridder, L. & Wagener, M. SyGMa: Combining Expert Knowledge and Empirical Scoring in the Prediction of Metabolites. ChemMedChem 3, 821–832 (2008).

MetaTrans : Litsa, E. E., Das, P. & Kavraki, L. E. Prediction of drug metabolites using neural machine translation. Chem. Sci. 11, 12777–12788 (2020).

MetaPredictor: in silico prediction of drug metabolites based on deep language models with prompt engineering

Publication

Pelletier R, Bourdais A, Fabresse N, Ferron PJ, Morel I, Gicquel T, Le Daré B. In silico and in vitro metabolism studies of the new synthetic opiate AP-237 (bucinnazine) using bioinformatics tools. Arch Toxicol. 2024 Jan;98(1):165-179. doi: 10.1007/s00204-023-03617-x. Epub 2023 Oct 15. PMID: 37839054.

Pelletier R, Le Daré B, Le Bouëdec D, Bourdais A, Ferron PJ, Morel I, Porée FH, Gicquel T. Identification, synthesis and quantification of eutylone consumption markers in a chemsex context. Arch Toxicol. 2024 Jan;98(1):151-158. doi: 10.1007/s00204-023-03615-z. Epub 2023 Oct 13. PMID: 37833490.