xenosite.forest

Python implementation of Metabolic Forest: enumerate explicit metabolite structures from reaction rules, and search pathways that connect a reactant to a putative product.

Site-of-metabolism prediction models (epoxidation, quinonation, Phase I, reactivity, and others) are on the web at xenosite.org. This package is the structure-enumeration engine, not those neural-network models.

If you use this software, please cite the Metabolic Forest paper (DOI and BibTeX below).

Install

uv add xenosite-forest

or

pip install xenosite-forest

Optional NetworkX helpers for building a metabolite graph:

uv add "xenosite-forest[network]"

Requires Python 3.10+ and RDKit.

Quick start

from rdkit import Chem
from xenosite.forest import bfs, rules, PhaseOneRS

# Pathway from ethanol to acetaldehyde
smiles, steps, mols = next(bfs(["CCO", "CC=O"], ruleset="PhaseOneRS"))
print(smiles)
print(steps)

# Enumerate hydroxylation products of propane
for site, products in rules.Hydroxylation().metabolites(Chem.MolFromSmiles("CCC")):
    print(site, [Chem.MolToSmiles(p) for p in products])

# Named Phase I ruleset
print(sorted({rule.name for rule in PhaseOneRS}))

A longer walkthrough is in examples/tutorial.ipynb. API notes are in docs/usage.md. Rulesets and their papers are in docs/rulesets.md.

Command line

xenosite-forest CCO CC=O --ruleset PhaseOneRS --depth 1

Useful flags: --all-paths, --depth N, --phase1 (Phase I site strings), --max N, --ruleset NAME.

Rulesets and papers

Pass these names to bfs(..., ruleset=...) or load_ruleset(...). Full rule lists, Rainbow colors/hex codes, aliases, and BibTeX are in docs/rulesets.md.

Rainbow colorblind-safe hex (Wong / Okabe–Ito, closest to the paper figures): SO Stable Oxygenation red #D55E00, UO Unstable Oxygenation orange #E69F00, DH Dehydrogenation green #009E73, HD Hydrolysis blue #56B4E9, RD Reduction purple #CC79A7.

Related single-rule papers: epoxidation (10.1021/acscentsci.5b00131), N-dealkylation (10.1021/acs.chemrestox.7b00191), UGT glucuronidation (10.1093/bioinformatics/btw350), glutathione reactivity (10.1021/acs.chemrestox.5b00017).

Documentation

• Rulesets and papers — every built-in ruleset, Rainbow colors, and publication BibTeX
• Usage — public API and pathway search
• Tutorial notebook — interactive walkthrough
• xenosite.org — XenoSite models for sites of metabolism and reactivity
• Source repository — code, issues, and releases

Import the package as xenosite.forest. xenosite is a PEP 420 namespace, so other xenosite.* packages can be installed alongside this one.

Citation

Please cite Metabolic Forest if you use this package:

Hughes, T. B.; Dang, N. L.; Kumar, A.; Flynn, N. R.; Swamidass, S. J. Metabolic Forest: Predicting the Diverse Structures of Drug Metabolites. J. Chem. Inf. Model. 2020, 60 (10), 4702–4716. DOI: 10.1021/acs.jcim.0c00360

BibTeX (copy and paste):

@article{Hughes2020MetabolicForest,
  title = {Metabolic Forest: Predicting the Diverse Structures of Drug Metabolites},
  author = {Hughes, Tyler B. and Dang, Na Le and Kumar, Ayush and Flynn, Noah R. and Swamidass, S. Joshua},
  journal = {Journal of Chemical Information and Modeling},
  volume = {60},
  number = {10},
  pages = {4702--4716},
  year = {2020},
  doi = {10.1021/acs.jcim.0c00360},
  url = {https://doi.org/10.1021/acs.jcim.0c00360},
  publisher = {American Chemical Society}
}

A machine-readable citation is also in CITATION.cff.

Development

git clone https://github.com/swamidasslab/xenosite-forest.git
cd xenosite-forest
uv sync --extra network --group dev
uv run pytest -n auto

Versioning comes from git tags via hatch-vcs (setuptools-scm). Tag a release as vX.Y.Z (for example v0.1.0). On that commit the version is X.Y.Z. On later untagged commits it becomes the next patch with a dev suffix and short commit, for example 0.1.1.dev3+gabc1234. Read it at runtime as xenosite.forest.__version__.

Pushing a v* tag runs .github/workflows/release.yml: tests must pass and the resolved version must be a clean X.Y.Z before a GitHub Release and PyPI upload. A red tag workflow means do not treat that tag as released. To block creating tags unless checks pass, add a GitHub Ruleset on refs/tags/v* that requires the release / test status checks.

One-time PyPI Trusted Publishing setup

No API token is stored in the repo. CI authenticates with Trusted Publishing (OIDC).

1. Create the GitHub repo swamidasslab/xenosite-forest and push main.

2. GitHub → Settings → Environments → create an environment named exactly pypi (optional: require reviewers before deploy).

3. On PyPI: add a pending trusted publisher (project does not need to exist yet):

   Field	Value
   PyPI project name	xenosite-forest
   Owner	swamidasslab
   Repository name	xenosite-forest
   Workflow name	release.yml
   Environment name	pypi

4. Tag a release (git tag -a v0.1.0 -m "0.1.0" && git push origin v0.1.0). The pypi-publish job uploads only after tests and build succeed.

For a dry run, register the same publisher on TestPyPI first and temporarily point the publish action at TestPyPI.

License

MIT. See LICENSE.