omicverse-single-cell-differential-abundance

OmicVerse Single-Cell Differential Abundance

Goal

Turn notebook-style OmicVerse differential cell-type abundance analysis into a reusable execution spine. Keep this skill separate from DEG because DCT has a different constructor, different branch-specific prerequisites, and different result shapes.

Quick Workflow

1. Inspect the input AnnData, the condition column, the cell-type column, and whether sample IDs and a usable embedding already exist.
2. Choose a backend before running anything: sccoda for the scCODA branch, milopy for the native Python Milo-like branch, or milo for the pertpy Milo branch.
3. For milopy and milo, make sure sample_key exists and use_rep points to an embedding already stored in obsm.
4. Construct ov.single.DCT(...) with explicit branch arguments, then run run(...).
5. For sccoda, do any posterior-specific follow-up such as set_fdr(...) only after the model has finished.
6. Collect results with get_results(...) and verify the branch-specific output columns before plotting or exporting.

Interface Summary

• ov.single.DCT(adata, condition, ctrl_group, test_group, cell_type_key, method='sccoda', sample_key=None, use_rep=None) initializes the wrapper.
• method branches are sccoda, milopy, and milo.
• sample_key is operationally required for the Milo-family branches because neighborhood counts are aggregated per sample.
• use_rep is required for milopy; current code also uses it for milo, even though only the milopy branch validates it eagerly.
• The constructor filters to the control and test labels immediately and reorders the condition categories.
• DCT.run(**kwargs) forwards kwargs only to the sccoda branch via run_nuts(...).
• milopy and milo ignore extra kwargs in current wrapper code and instead run fixed neighborhood-testing logic.
• DCT.get_results(mix_threshold=0.6) returns a scCODA effect table for sccoda, or neighborhood-level Milo tables for milopy and milo.
• mix_threshold only affects the Milo-family branches by relabeling low-purity neighborhoods as Mixed.

Stage Selection

• Use method='sccoda' when the user wants compositional Bayesian inference and is prepared for posterior sampling and FDR tuning.
• Use method='milopy' when the user wants the native Python Milo-like path and already has a valid embedding such as PCA or Harmony.
• Use method='milo' only when the pertpy Milo branch is specifically required.
• Keep diagnostic plots and beeswarm visualizations optional; they are downstream reporting on top of the DCT results, not the reusable contract itself.

Input Contract

• Start from an AnnData object with condition labels and cell-type annotations in obs.
• Provide control and test labels that exist in the condition column.
• For sccoda, provide a sample identifier because the scCODA preparation step loads cell-level data into a sample-aware modality.
• For milopy and milo, provide both sample_key and use_rep.
• Ensure the embedding named by use_rep already exists in adata.obsm.

Minimal Execution Patterns

import omicverse as ov

dct = ov.single.DCT(
    adata,
    condition="condition",
    ctrl_group="Control",
    test_group="Salmonella",
    cell_type_key="cell_label",
    method="sccoda",
    sample_key="batch",
)
dct.run(num_samples=5000, num_warmup=500)
res = dct.get_results()

dct = ov.single.DCT(
    adata,
    condition="condition",
    ctrl_group="Control",
    test_group="Salmonella",
    cell_type_key="cell_label",
    method="milopy",
    sample_key="batch",
    use_rep="X_harmony",
)
dct.run()
res = dct.get_results(mix_threshold=0.6)

Constraints

• Do not assume one abundance backend can replace another without changing the input contract.
• Do not hide method, sample_key, or use_rep; those choices control materially different code paths.
• Do not pass num_samples or num_warmup as if they affect the Milo-family branches; current wrapper code only forwards kwargs to sccoda.
• Do not claim that neighborhood purity relabeling matters for sccoda; mix_threshold only changes the Milo-family result table.
• Keep smoke and acceptance commands shell-agnostic. Do not rely on zsh-specific syntax, shell startup files, or shell-only features when a direct ${PYTHON} script.py command is enough.
• Do not put local paths or environment names into the reusable instructions.

Validation

• Check that the control and test labels both remain after constructor filtering.
• For sccoda, check that get_results() returns an effect table and that any FDR adjustment is applied after model fitting.
• For milopy or milo, check that the result table includes neighborhood annotation columns and abundance statistics such as FDR-like outputs.
• Check that the embedding named by use_rep existed before construction.
• If only one representative branch was run as a smoke test, say which branch was validated and which branches were source-grounded only.

Resource Map

• Use the branch selection notes when choosing between scCODA and the Milo-family branches.
• Use the source grounding notes when you need live signatures, current branching behavior, or branch-specific caveats.
• Use the notebook map when tracing which tutorial cells became which reusable instruction.
• Use the compatibility notes when notebook prose and current wrapper behavior differ.