Usage:

java -jar BioTransformer3.0.jar -k <BioTransformer Task> -b <BioTransformer Option> [-ismi, -imol, or -isdf <Input file>] [-imol, or -isdf <Output>] [-s <Number of steps>] [-a <Annotate>] [-m <Masses>] [-r <Masses>] [-f <Formulas>] [-q <Sequence>] [-cm <Cyp450 Mode>]

This is the version 3.0.0 of BioTransformer. BioTransformer is a software tool that predicts small molecule metabolism in mammals, their gut microbiota, as well as the soil/aquatic microbiota. BioTransformer also assists scientists in metabolite identification, based on the metabolism prediction.

-a,--annotate Search PuChem for each product, and annotate with CID and synonyms

-b,--btType <BioTransformer Option> The type of description: Type of biotransformer - EC-based (ecbased), CYP450 (cyp450), Phase II (phaseII), Human gut microbial (hgut), human super transformer* (superbio, or allHuman), Environmental microbial (envimicro).

-cm, cyp450mode CYP450 prediction Mode here: 1) CypReact + BioTransformer rules; 2) CyProduct only; 3) Combined: CypReact + BioTransformer rules + CyProducts. Default mode is 1.

-h,--help Prints the usage.

-ismi, --ismiles < Input > Read the input as a single molecule in SMILES format

-imol, --molinput <Input file> Read the input as a single molecule in the specified MOL format

-isdf, --sdfinput <Input file> Read the input from the specified SDF format

-k, --task <BioTransformer Task> The task to be permed: pred for prediction, or cid for compound identification

-m,--mList Given the starting compound(s), Find all their metabolites with the specified masses, and show a metabolism pathway. A whitespace-separated list of masses is expected.

-ocsv, --csvoutput <Output file> Save the results into the specified CSV file

-osdf, --sdfoutput <Output file> Save the results into the specified SDF file

-f,--formulas <formulas> Semicolon-separated list of formulas of compounds to identify
-s,--nsteps <Number of steps> The number of steps for the prediction. This option can be set by the user for the EC-based, CYP450, Phase II, and Environmental microbial biotransformers. The default value is 1.

-q, --bsequence <Sequence> Ordered Sequence of biotransformation steps. Semi-colon separated pairs of biotransformer types and corresponding number of steps to be simulated.

-t,--mTolerance Mass tolerance for metabolite identification (default is 0.01).

(* ) While the 'superbio' option runs a set number of transformation steps in a pre-defined order (e.g. deconjugation first, then Oxidation/reduction, etc.), the 'allHuman' option predicts all possible metabolites from any applicable reaction(Oxidation, reduction, (de-)conjugation) at each step.

(** ) For the environmental microbial biodegradation, all reactions (aerobic and anaerobic) are reported, and not only the aerobic biotransformations (as per default in the EAWAG BBD/PPS system).

Note: If you need to run multiple very complex compounds, you may need to increase the JVM MaxHeapSize value

Examples:

1) To predict the biotransformation of a molecule from an SDF input using the human super transformer (option superbio) and annotate the metabolites with names and database IDs (from PubChem), run

  java -jar biotransformer-3.0.0.jar -k pred -b superbio -isdf -i #{input file name} -osdf #{output file} -a.

2) To predict the 2-step biotransformation of Thymol (a monoterpene) using the human super transformer (option allHuman) using the SMILES input, cypMode = 3 (combined mode), and saving to a CSV file, run

  java -jar biotransformer-3.0.0.jar  -k pred -b allHuman -ismi "CC(C)C1=CC=C(C)C=C1O" -ocsv #{replace with output file name} -s 2 -cm 3

Currently, the outputfile is SDF per default.

3) Identify all human metabolites (max depth = 2) of Epicatechin ("O[C@@H]1CC2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C(O)=C1") with masses 292.0946 Da and 304.0946 Da, with a mass tolerance of 0.01 Da. Provide an annotation (Common name, synonyms, and PubChem CID), when available.

  java -jar biotransformer-3.0.0.jar  -k cid -b allHuman -ismi "O[C@@H]1CC2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C(O)=C1" -osdf #{replace with output file name} -s 2 -m "292.0946;304.0946" -t 0.01 -a

- DO NOT forget the quotes around the SMILES string or the list of masses.

4) Simulate an order sequence of metabolism of Atrazine ("CCNC1=NC(=NC(=N1)Cl)NC(C)C"), starting with two steps of Cyp450 oxidation, followed by one step of conjugation.

java -jar biotransformer-3.0.0.jar -ismi "CCNC1=NC(=NC(=N1)Cl)NC(C)C" -osdf ~/atrazine-sequence.sdf -k pred -q "cyp450:2; phaseII:1"

To report issues, provide feedback, or ask questions, please send an e-mail the following address: djoumbou@ualberta.ca