pkflow 0.1.0a6

Pharmacometric modeling workflow CLI

PKflow

A composable command-line workflow tool for pharmacometric modeling.

PKflow turns the run → diagnose → compare → report loop of population PK/PD modeling into a handful of scriptable commands. Fit a NONMEM model, collect its results into a tidy, file-based format, and generate goodness-of-fit plots, VPCs, bootstrap confidence intervals, shrinkage tables, η–covariate plots, and a shareable report — all from the terminal or as a Python library.

It is a clean-room Python rewrite of the ideas behind the classic Pirana workbench, with three deliberate design choices:

• File-based, not a database. Every run is a self-contained directory (results.yaml + parquet sidecars) — diffable, reproducible, and git-friendly.
• A thin backend protocol. Modeling-engine specifics live behind a small parse / run / collect interface. Today that backend is NONMEM (via pharmpy); the diagnostics, workflows, and report layers are engine-agnostic.
• Pure functions you can test. The statistics (VPC binning, bootstrap CIs, shrinkage, comparison tables) are pure and unit-tested without needing NONMEM.

Status: early alpha (0.1.0a6). The NONMEM workflow below works end-to-end against a real nmfe binary. APIs may still change.

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Table of contents

• Install
• Quickstart
• Configuration
• Examples — one per feature
  • 1. Run a model
  • 2. Inspect saved results
  • 3. Compare runs
  • 4. Bootstrap confidence intervals
  • 5. Goodness-of-fit plots
  • 6. Visual Predictive Check (VPC)
  • 7. η / ε shrinkage
  • 8. η–covariate plots
  • 9. Reports (md / html / docx / pdf)
  • 10. Use it as a Python library
• Run directory layout
• Architecture
• Development
• Contributing
• Roadmap
• Citation
• Acknowledgements
• Author
• License

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Install

Requires Python ≥ 3.10.

pip install pkflow

To actually run models you also need:

• A NONMEM installation with an nmfe script on PATH (or point at it via pkflow config set nmfe <path> — see Configuration).
• pandoc (system package) — only for report --format html|docx|pdf. Markdown reports and everything else need no extra tooling.
• A PDF engine — only for report --format pdf. pkflow drives whichever it finds first: weasyprint (pip install weasyprint), wkhtmltopdf, or a LaTeX engine (tectonic / xelatex / pdflatex).

Python dependencies (installed automatically): pharmpy-core, pandas, pyarrow, plotnine, scikit-misc, jinja2, pyyaml, typer, tomli-w.

---

Quickstart

# 0. Tell pkflow where NONMEM lives (once, stored in ~/.config/pkflow/config.toml)
pkflow config set nmfe /opt/nm760/run/nmfe76

# 1. Fit a model — creates runs/<name>_<timestamp>/
pkflow run model.ctl

# 2..N. Downstream commands default to the LAST successful run, so you can
#       drop the run-dir argument entirely:
pkflow show
pkflow diagnose
pkflow vpc
pkflow shrinkage
pkflow report --format pdf --gof

Every command is independent and operates on a saved run directory, so you can re-run, re-collect, and re-diagnose without re-fitting. Pass an explicit <run_dir> whenever you want a run other than the most recent one:

pkflow show      runs/model_20260609_120000/
pkflow diagnose  runs/model_20260609_120000/

---

Configuration

pkflow reads configuration from two layered TOML files (last wins):

built-in defaults  <  ~/.config/pkflow/config.toml  <  ./pkflow.toml  <  CLI flags

Manage it with pkflow config — no need to hand-edit files:

pkflow config show                              # resolved values + their source
pkflow config set nmfe /opt/nm760/run/nmfe76    # user-global (default scope)
pkflow config set --project runs_dir output     # project-local ./pkflow.toml
pkflow config get nmfe
pkflow config unset nmfe
pkflow config path                              # where the user file lives

Key	Default	Meaning
backend	nonmem	Modeling engine (only NONMEM today)
executor	local	Local subprocess runner
nmfe	nmfe75	Path to your NONMEM nmfe script
runs_dir	runs	Where run directories are created

Use the user scope for machine-wide settings like the nmfe path, and the project scope (--project, writes ./pkflow.toml) for per-study overrides. Per-invocation flags such as --backend / --runs-dir win over both.

---

Examples

The examples below use a 2-compartment IV model warfarin.ctl. Replace it with your own control stream — PKflow reads $INPUT, $DATA, parameter blocks, and result files (.lst, .ext, .phi) through pharmpy.

1. Run a model

pkflow run warfarin.ctl

→ runs/warfarin_20260609_120000
status: ok  ofv: 1234.56  (21.9s)

run creates an isolated run directory, copies the dataset in and rewrites $DATA so models with relative data paths just work, executes NONMEM, then collects everything into results.yaml + parquet sidecars (parameters, predictions, η estimates, covariates).

2. Inspect saved results

pkflow show runs/warfarin_20260609_120000/

run      : warfarin_20260609_120000
backend  : nonmem
status   : ok
ofv      : 1234.56
aic/bic  : 1250.56 / 1278.10
cond #   : 18.3

parameters:
     name   type  estimate      se  rse_pct
       CL  theta     0.134  0.0042      3.1
       V1  theta     8.110  0.2100      2.6
        Q  theta     0.220  0.0180      8.2
 OMEGA_1_1  omega     0.091  0.0150     16.4

show reads only the saved files — no NONMEM needed. Use pkflow collect <run_dir> to re-parse the NONMEM output of an existing run without re-fitting.

3. Compare runs

Rank competing models side by side. ΔOFV is relative to the best (lowest) run; failed runs are excluded from the "best" calculation.

pkflow compare runs/base_*/ runs/covCL_*/ runs/covCL_V_*/ --sort ofv --gof

          run_id status     ofv  delta_ofv  n_params     aic     bic  condition_number
covCL_V_20260609     ok  1208.9        0.0         9  1226.9  1236.9              18.3
  covCL_20260609     ok  1210.2        1.3         7  1224.2  1234.2              18.3
   base_20260609     ok  1234.5       25.6         5  1244.5  1254.5              18.3

→ compare/comparison.csv
→ compare/compare_gof.png      # overlaid DV-vs-PRED, colored by run

4. Bootstrap confidence intervals

Nonparametric case-resampling bootstrap: subjects are resampled with replacement (and relabeled to keep duplicates distinct), the model is refit on each replicate, and percentile CIs are reported. Non-converged replicates are excluded and counted.

pkflow bootstrap warfarin.ctl --n 200 --ci 0.95

→ runs/warfarin_20260609_121500  (200 replicates)
converged: 196/200

     name  original_est  boot_median   boot_se   ci_lo   ci_hi  n_success
       CL         0.134        0.135    0.0051   0.125   0.145        196
       V1         8.110        8.090    0.2400   7.640   8.580        196
 OMEGA_1_1         0.091        0.087    0.0190   0.052   0.128        196

→ runs/.../bootstrap/bootstrap_summary.csv

Per-replicate run directories are cleaned up automatically; the summary and the raw per-replicate estimates (replicate_params.parquet) are kept.

5. Goodness-of-fit plots

The standard 4-panel GOF (DV-vs-PRED, DV-vs-IPRED, CWRES-vs-PRED, CWRES-vs-TIME), rendered with plotnine:

pkflow diagnose runs/warfarin_20260609_120000/

  runs/.../diagnostics/dv_vs_pred.png
  runs/.../diagnostics/dv_vs_ipred.png
  runs/.../diagnostics/cwres_vs_pred.png
  runs/.../diagnostics/cwres_vs_time.png
→ 4 plot(s) in runs/.../diagnostics

GOF needs a $TABLE with DV PRED IPRED CWRES TIME written to an sdtab-style file so PKflow can find it.

6. Visual Predictive Check (VPC)

PKflow converts the fitted model to a simulation ($SIMULATION with N subproblems), runs it, bins observations by time, and overlays the observed 5/50/95 percentiles on the simulated prediction intervals.

pkflow vpc runs/warfarin_20260609_120000/ --n-sim 500 --n-bins 10

→ runs/.../diagnostics/vpc.png    (+ vpc.csv with the binned percentiles)

7. η / ε shrinkage

A shrinkage table (flagging values above a threshold, default 30%) plus a faceted histogram of the individual η estimates.

pkflow shrinkage runs/warfarin_20260609_120000/ --threshold 0.30

parameter kind  shrinkage  shrinkage_pct   high
    ETA_1  eta     0.0868          8.68   False
    ETA_2  eta     0.4171         41.71    True
    ETA_3  eta     0.6388         63.88    True

→ runs/.../diagnostics/shrinkage_table.csv
→ runs/.../diagnostics/eta_distributions.png

8. η–covariate plots

Scatter of each η against each subject-level covariate, with a linear trend. Covariates are auto-detected (constant-within-subject, varying across subjects); override with --cov.

# auto-detect covariates
pkflow etacov runs/warfarin_20260609_120000/

# or name them explicitly
pkflow etacov runs/warfarin_20260609_120000/ --cov WT --cov SEX --cov AGE

→ runs/.../diagnostics/eta_covariates.png   (facet grid: η rows × covariate cols)
→ runs/.../diagnostics/eta_covariates.csv

9. Reports (md / html / docx / pdf)

Assemble fit summary, parameter table, shrinkage, any bootstrap result, and the diagnostic plots into one document. Markdown is the canonical render; HTML, Word, and PDF are produced via pandoc.

# Markdown (no extra dependencies)
pkflow report runs/warfarin_20260609_120000/ --format md

# Word document, generating GOF plots first and embedding them
pkflow report runs/warfarin_20260609_120000/ --format docx --gof

# PDF (needs a PDF engine: weasyprint / wkhtmltopdf / a LaTeX engine)
pkflow report --format pdf --gof          # defaults to the last run

# HTML
pkflow report --format html

→ runs/.../report/report.pdf

docx/html/pdf require pandoc on PATH; pdf additionally needs a PDF engine — pkflow auto-detects weasyprint, wkhtmltopdf, tectonic, xelatex, or pdflatex (in that order) and gives a clear, actionable error if none is installed.

10. Use it as a Python library

Everything the CLI does is available as importable functions. The statistics are pure — feed them a Results object (from a saved run or constructed in memory):

from pathlib import Path
from pkflow import backends
from pkflow.executors import LocalExecutor
from pkflow.model import Results
from pkflow.compare import build_table
from pkflow.diagnostics import save_gof, shrinkage_table
from pkflow.workflows import bootstrap

be = backends.get("nonmem")
ex = LocalExecutor({"nmfe": "/opt/nm760/run/nmfe76"})

# parse → run → collect
model  = be.parse(Path("warfarin.ctl"))
handle = be.run(model, Path("runs/wf"), ex)
res    = be.collect(model, Path("runs/wf"), handle)
res.save(Path("runs/wf"))

# load a saved run later
res = Results.load(Path("runs/wf"))

# pure analytics
table = build_table([Results.load(p) for p in Path("runs").glob("*/")])
shr   = shrinkage_table(res, threshold=0.3)
save_gof(res, Path("runs/wf/diagnostics"))

# a full bootstrap workflow
boot = bootstrap(model, res, be, ex, Path("runs/wf"), n=200, seed=1234)
print(boot.summary)

---

Run directory layout

A run directory is the unit of reproducibility:

runs/warfarin_20260609_120000/
├── results.yaml            # fit metadata: status, ofv, aic/bic, cond#, shrinkage
├── parameters.parquet      # estimates + SE + RSE%
├── predictions.parquet     # $TABLE output (DV/PRED/IPRED/CWRES/...)
├── etas.parquet            # individual η estimates
├── covariates.parquet      # per-subject covariates
├── warfarin.ctl            # the control stream that was run
├── diagnostics/            # GOF, VPC, shrinkage, η-covariate PNGs + CSVs
├── bootstrap/              # bootstrap_summary.csv + replicate_params.parquet
└── report/                 # report.md / .html / .docx

---

Architecture

pkflow/
├── cli.py              # typer entrypoint — every command is a thin wrapper
├── config.py           # pkflow.toml loader
├── compare.py          # cross-run table + overlaid GOF (pure functions)
├── model/
│   ├── base.py         # backend-agnostic Model
│   └── results.py      # unified Results + save/load (yaml + parquet)
├── backends/
│   ├── base.py         # Backend protocol: parse / run / collect / simulate
│   └── nonmem.py       # pharmpy-backed NONMEM implementation
├── executors/
│   └── local.py        # local subprocess runner
├── diagnostics/
│   ├── gof.py          # 4-panel goodness-of-fit
│   ├── vpc.py          # backend-agnostic VPC (compute + plot)
│   └── shrinkage.py    # shrinkage table, η distributions, η-covariate plots
├── workflows/
│   └── bootstrap.py    # case-resampling bootstrap (pure stats + orchestrator)
└── report/
    ├── render.py       # context builder + Jinja2 markdown + pandoc convert
    └── templates/      # run_report.md.j2

Extending it is meant to be small:

• A new backend (e.g. another estimation engine) = one file implementing parse / run / collect.
• A new executor (e.g. Slurm/SGE) = one file implementing submit / wait.

The diagnostics, comparison, bootstrap, and report layers consume the unified Results object and don't care which engine produced it.

---

Development

pip install -e ".[dev]"
python -m pytest          # full suite

The test suite covers every module. Pure-function tests (config, results, compare, bootstrap, VPC math, shrinkage, report rendering) run without NONMEM using in-memory Results; NONMEM-dependent paths are exercised with a real .mod template and stubbed/faked boundaries. Pandoc-dependent report tests skip automatically when pandoc is absent.

---

Contributing

Contributions are welcome! Please see CONTRIBUTING.md for details. In short:

1. Open an issue to discuss bugs or feature ideas before large changes.
2. Follow test-driven development — add a failing test first, then the implementation. Keep statistics as pure functions where possible.
3. Run python -m pytest and make sure the suite is green before opening a PR.

---

Roadmap

• Categorical-covariate boxplots in η–covariate plots
• Cluster executors (slurm, sge)
• Additional report sections and templating hooks

The backend protocol is intentionally general, but the project is focused on NONMEM for now.

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Citation

If you use PKflow in your research, please cite it:

@software{zhang_pkflow,
  author  = {Zhang, Yufeng},
  title   = {PKflow: A composable command-line workflow tool for pharmacometric modeling},
  year    = {2026},
  url      = {https://github.com/kinginsun/pkflow}
}

Acknowledgements

PKflow stands on the shoulders of excellent open-source work:

• pharmpy — NONMEM control-stream parsing and result handling.
• plotnine — grammar-of-graphics plotting for all diagnostics.
• pandas, Typer, Jinja2, and pandoc.
• The original Pirana workbench, whose workflow inspired this rewrite.

Author

Yufeng Zhang School of Pharmacy, The Chinese University of Hong Kong (CUHK) Contact: [e-mail]

License

Released under the MIT License — see LICENSE.

MIT License

Copyright (c) 2026 Yufeng Zhang

PKflow is an independent Python project and is not affiliated with the original Pirana software.