Shedding Hub

The Shedding Hub collates data and statistical models for biomarker shedding (such as viral RNA or drug metabolites) in different human specimen (such as stool or sputum samples). Developing wastewater-based epidemiology into a quantitative, reliable epidemiological monitoring tool motivates the project.

Datasets are extracted from appendices, figures, and supplementary materials of peer-reviewed studies. Each dataset is stored as a .yaml file and validated against our data schema to verify its integrity.

📊 Getting the Data

You can obtain the data by downloading it from GitHub. We also provide a convenient Python package so you can download the most recent data directly in your code or obtain a specific version of the data for reproducible analysis. Install the package by running pip install shedding-hub from the command line. The example below downloads the data from Wölfel et al. (2020) as of the commit 259ca0d.

>>> import shedding_hub as sh

>>> sh.load_dataset('woelfel2020virological', ref='259ca0d')
{'title': 'Virological assessment of hospitalized patients with COVID-2019',
 'doi': '10.1038/s41586-020-2196-x',
 ...}

You can also check whether a paper is already in the dataset collection using the check_dataset function.

>>> sh.check_dataset(doi='10.1038/s41586-020-2196-x')
True

>>> sh.check_dataset(title='Virological assessment of hospitalized patients with COVID-2019')
True

📈 Analyzing the Data

The package provides statistical summaries and visualization tools to analyze shedding patterns across studies.

Statistical Summaries

Calculate per-participant shedding statistics including duration, peak values, and clearance status.

>>> data = sh.load_dataset('woelfel2020virological', ref='259ca0d')
>>> summary = sh.calc_shedding_summary(data, specimen='sputum')
>>> list(summary.columns)  # doctest: +NORMALIZE_WHITESPACE
['participant_id', 'biomarker', 'specimen', 'value_type', 'reference_event',
 'first_positive_time', 'last_positive_time', 'shedding_duration', 'peak_value',
 'peak_time', 'n_positive', 'n_negative', 'n_total', 'clearance_status', 'clearance_time']

Analyze detection rates over time with confidence intervals.

>>> detection = sh.calc_detection_summary(data, specimen='sputum', time_bin_size=7)
>>> list(detection.columns)
['time', 'n_tested', 'n_positive', 'n_negative', 'proportion', 'ci_lower', 'ci_upper']

Compare shedding patterns across multiple datasets.

>>> data1 = sh.load_dataset('woelfel2020virological', local='./data')
>>> data2 = sh.load_dataset('kimse2020viral', local='./data')
>>> comparison = sh.compare_datasets([data1, data2], specimen='sputum', value='concentration')
>>> list(comparison.columns)  # doctest: +NORMALIZE_WHITESPACE
['dataset_id', 'n_participants', 'n_measurements', 'pct_positive',
 'median_shedding_duration', 'iqr_shedding_duration', 'median_peak_value',
 'iqr_peak_value', 'median_peak_time', 'pct_cleared', 'median_clearance_time']

Simulating Shedding

Simulate shedding trajectories for synthetic infected individuals — intended for agent-based models of wastewater surveillance. Browse the catalog of fitted estimates, pick one study or an ensemble across studies, then simulate.

Full documentation — a tutorial, the modeling methods, and a generated API reference covering every public name with a worked example — is at shedding-hub.readthedocs.io.

examples/simulating-shedding.md walks through the whole workflow, including how to override the default choice and what the estimates do not support. It refits nothing and runs in seconds. It is a jupytext notebook, like the extraction scripts, so open it directly in Jupyter or convert it first:

jupytext --to ipynb examples/simulating-shedding.md
jupyter lab examples/simulating-shedding.ipynb

The examples in this section run in CI as doctests against the shipped catalog (shedding_hub/data/shedding_catalog.yaml), deliberately not skipped, so that documentation drift fails loudly: if a future catalog rebuild gates out the woelfel2020virological stool gamma fit used below, update the dataset_id/analyte/model/ensemble filters to a fit that still exists rather than re-adding +SKIP.

>>> import numpy as np
>>> import shedding_hub as sh
>>> catalog = sh.load_shedding_catalog()
>>> catalog.table[['dataset_id', 'specimen', 'model', 'peak_day']].head()  # doctest: +SKIP
>>> fit = catalog.select(
...     dataset_id='woelfel2020virological', analyte='stool', model='gamma'
... )
>>> traj = sh.simulate_shedding(
...     fit, n_individuals=100, times=np.arange(0, 30), seed=42
... )
>>> list(traj.columns)
['individual_id', 'time', 'log10_value', 'value', 'detected', 'source_dataset_id']

Picking a fit by hand means naming five keys — biomarker, specimen, reference event, unit and model — and those keys cut the catalog into 82 groups, 71 of which hold a single study. To see the choice, and to have it made for you:

>>> import shedding_hub as sh
>>> options = sh.shedding_options(biomarker='SARS-CoV-2', specimen='stool')
>>> list(options.columns)
['biomarker', 'specimen', 'reference_event', 'event_class', 'unit', 'n_unit_studies', 'model', 'n_studies', 'n_subjects', 'n_measurements', 'rank']
>>> source = sh.shedding_for('SARS-CoV-2', 'stool')
>>> source.selection.picked['event_class']
'landmark'

shedding_for takes rank 1 from shedding_options, preferring a reference event that can be placed on an infection timeline, then the unit most studies report for that biomarker and specimen, then a model that resolves the rise, then the weight of evidence. Pass model=, unit= or reference_event= to pin any of them, and read source.selection for what was chosen and what it beat.

source.selection is a Selection: picked (the winning group's keys and counts), passed_over (the rest of the ranked table), reason (the rule that decided it) and analytes (which analyte was taken from each study offering more than one). str(selection) summarises all of it in one line:

>>> print(sh.shedding_for('SARS-CoV-2', 'stool').selection)
picked symptom onset / gc/mL / gamma (2 study/studies, 16 subjects); ...

Three models are available. exponential is a pure decay from the reference event. gamma rises and falls after it. gamma_shifted is the same rise and fall with a fitted onset t0, so its support starts when shedding started rather than at the reference event:

c(t) = c0 * (t - t0)**b0 * exp(-a0 * (t - t0)),   t > t0

Both rise-and-fall models are only fitted where a rise was actually observed — at least half of a study's subjects must have their peak reading later than their first sample, since otherwise the rise parameter is unidentifiable. catalog.skipped records why anything is missing.

gamma_shifted exists because gamma is undefined at t <= 0 and therefore discards every reading there, including 26,023 detected measurements at exactly the reference event. It is offered only for analytes that have a detected reading at or before their reference event; without one, t0 has nothing to locate and merely absorbs curve shape.

Do not compare gamma and gamma_shifted by AIC. Where gamma_shifted is admitted it is fitted to more observations than gamma — 2072 against 1679 for kissler2021viral — and AIC is only comparable across models fitted to the same data. The choice between them is made by data availability, which is what the gate above encodes, not by fit statistic. Comparing exponential against either is likewise only meaningful when n_measurements matches.

Pass incubation_period to express times as days since infection rather than days since the study's reference event:

>>> traj = sh.simulate_shedding(
...     fit, n_individuals=100, times=np.arange(0, 30),
...     incubation_period=5.0, seed=42
... )
>>> traj.attrs['time_origin']
'infection'

The gamma curve is undefined at or before the reference event, so any row whose time falls there comes back as NaN with detected=False — including, when incubation_period shifts the timeline, every early times entry that still falls within the incubation window. pandas skips NaN when summing, so aggregating simulated load across a cohort is safe by default, but account for it if you do your own arithmetic on log10_value or value.

To pool evidence across studies, build an ensemble. Each simulated individual is drawn from one contributing study, so between-study variation is preserved:

>>> ensemble = catalog.ensemble(
...     biomarker='SARS-CoV-2', specimen='stool',
...     reference_event='symptom onset', unit='gc/mL', model='gamma',
... )
>>> traj = sh.simulate_shedding(
...     ensemble, n_individuals=1000, times=np.arange(0, 30), seed=42
... )

Estimates come from a censored maximum-likelihood fit, so negative measurements inform the fit rather than being discarded. Because the two-stage fit does not shrink individual estimates toward the population mean, simulated cohorts are somewhat more dispersed than reality.

That over-dispersion matters when a few agents can dominate a total. Pass dispersion below 1 to scale the between-subject covariance by dispersion ** 2, narrowing the cohort's spread while leaving its centre and correlation structure alone:

>>> traj = sh.simulate_shedding(
...     fit, n_individuals=1000, times=np.arange(0, 30),
...     dispersion=0.7, seed=42,
... )

The default of 1.0 simulates the fitted population exactly as estimated. There is no automatic way to choose a lower value — it is a judgement about how much of the fitted spread is real estimation noise rather than genuine heterogeneity. What makes shrinkage the only direction offered is that the two-stage bias runs one way: the fitted spread is too wide, never too narrow.

For how the estimates are produced, what they mean, and where they should not be trusted, see docs/modeling-methods.md. make parameters writes the fitted parameters for every dataset to docs/shedding_parameters.json (reusable: each record carries the population mean and covariance, so it can be simulated from without refitting) and docs/shedding_parameters.csv (flat, one row per fit).

Visualization

Plot individual shedding trajectories over time.

>>> fig = sh.plot_time_course(data, specimen='sputum')

Visualize aggregate shedding patterns with mean or median trajectories and confidence bands.

>>> fig = sh.plot_mean_trajectory(data, specimen='sputum', central_tendency='median')

Generate heatmaps to compare shedding across participants.

>>> fig = sh.plot_shedding_heatmap(data, specimen='sputum')

Create Kaplan-Meier clearance curves for survival analysis.

>>> from shedding_hub.viz import plot_clearance_curve
>>> fig = plot_clearance_curve(data, specimen='sputum')

Compare the fitted curves themselves across studies. Each panel holds one (biomarker, specimen, unit, reference_event) group, since curves disagreeing on either axis cannot honestly be overlaid; colour identifies the study and linestyle the model. The stretch of each curve before a study's median first observation is faded, marking where the curve is functional form rather than measurement — for half the catalog's gamma fits, that is the entire rise phase.

>>> fig = sh.plot_catalog_fits(
...     catalog, biomarker='SARS-CoV-2', unit='gc/mL',
...     reference_event='symptom onset',
... )

To judge a single fit rather than compare several, plot it against the data behind it. The points come from the fitter's own view of the dataset, so the page shows exactly what the fit saw — the same censoring limit, the same excluded subjects — and censored readings are drawn on the limit rather than dropped. The estimated parameters and the fit's context sit in the legend.

>>> fig = sh.plot_fit_diagnostic(fit, data1)

Behind the observations it shades the central 5–95% of a simulated cohort drawn from the fitted population, because the median individual alone says nothing about whether the spread is right — which is most of what separates a usable fit from an unusable one. Pass dispersion to see the narrowed cohort, or show_band=False to omit it.

Measurements the fitter discarded are drawn too, marked as excluded rather than as data the curve should explain. The gamma model is undefined at t <= 0, so readings there are dropped — 391 of them for kissler2021viral — and a page that drew nothing would imply the study never sampled before its reference event.

make review renders every fit in the catalog this way into a single shedding_catalog_review.pdf, one page each. make review_range writes a second PDF shading the full range of the simulated cohort rather than its central 90%, with the 95% interval drawn inside it as two dashed lines and the y axis widened to fit — what each fit considers possible rather than typical. A range is also a property of how many individuals were drawn, which is why each page names its draw count.

To judge how much the over-extrapolation gate matters, rebuild the catalog at a different threshold and render it:

python scripts/build_shedding_catalog.py --max-peak-above-observed 2 \
    --output shedding_catalog_gate2.yaml
python scripts/build_catalog_review.py --catalog shedding_catalog_gate2.yaml \
    --output shedding_catalog_review_gate2.pdf

🤝 Contributing

Thank you for contributing your data to the Shedding Hub and supporting wastewater-based epidemiology! If you hit a bump along the road, create a new issue and we'll sort it out together.

We use pull requests to add and update data, allowing for review and quality assurance. Learn more about the general workflow here. To contribute your data, follow these easy steps (if you're already familiar with pull requests, steps 2 and 3 are for you):

1. Create a fork of the Shedding Hub repository by clicking here and clone the fork to your computer. You only have to do this once.
2. Create a new my_cool_study/my_cool_study.yaml file in the data directory and populate it with your data. See here for a comprehensive example from Wölfel et al. (2020). A minimal example for studies with a single analyte (e.g., SARS-CoV-2 RNA concentration in stool samples) is available here, and a minimal example for studies with multiple analytes (e.g., crAssphage RNA concentration in stool samples and caffeine metabolites in urine) is available here.
3. Optionally, if you have a recent version of Python installed, you can validate your data to ensure it has the right structure before contributing it to the Shedding Hub.
   • Run pip install -r requirements.txt from the command line to install all the Python packages you need.
   • Run pytest from the command line to validate all datasets, including the one you just created.
4. Create a new branch by running git checkout -b my_cool_study. Branches let you isolate changes you are making to the data, e.g., if you're simultaneously working on adding multiple studies–much appreciated! You should create a new branch from the main branch for each dataset you contribute; see here for more information.
5. Add your changes by running git add data/my_cool_study/my_cool_study.yaml and commit them by running git commit -m "Add data from Someone et al. (20xx).". Feel free to pick another commit message if you prefer.
6. Push the dataset to your fork by running git push origin my_cool_study. This will send the data to GitHub, and the output of the command will include a line Create a pull reuqest for 'my_cool_study' on GitHub by visiting: https://github.com/[your-username]/shedding-hub/pull/new/my_cool_study. Click on the link and follow the next steps to create a new pull request.

Congratulations, you've just created your first pull request to contribute a new dataset! We'll now review the changes you've made to make sure everything looks good. Once any questions have been resolved, we'll merge your changes into the repository. You've just contributed your first dataset to help make wastewater-based epidemiology a more quantitative public health monitoring tool–thank you!