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spatial-deconv

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Load when deconvolving spot-level cell-type proportions on a Visium-style spatial AnnData using a labelled scRNA reference (FlashDeconv / Cell2location / RCTD / DestVI / Tangram / others). Skip when each spot is a single cell already (Xenium / MERFISH — use spatial-annotate) or for tissue-domain detection (use spatial-domains).

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spatial-deconv

When to use

The user has a Visium-style multi-cell-per-spot spatial AnnData PLUS a labelled scRNA reference AnnData and wants per-spot cell-type proportions. Eight backends:

  • flashdeconv (default) — ultra-fast O(N) CPU sketching. No GPU.
  • cell2location — Bayesian deep learning with spatial priors (--cell2location-n-epochs, --cell2location-detection-alpha, --cell2location-n-cells-per-spot). Requires scvi-tools + cell2location + torch.
  • rctd — Robust Cell Type Decomposition (R / spacexr).
  • destvi — multi-resolution VAE (--destvi-n-epochs, --destvi-n-hidden / --destvi-n-latent / --destvi-n-layers). Requires scvi-tools + torch.
  • stereoscope — two-stage probabilistic VAE (--stereoscope-learning-rate). Requires scvi-tools + torch.
  • tangram — gradient-based mapping (--tangram-n-epochs, --tangram-learning-rate). Requires tangram.
  • spotlight — NMF-based with marker-gene priors (--spotlight-n-top, --spotlight-min-prop, --spotlight-weight-id).
  • card — Conditional Autoregressive R-based deconvolution.

For single-cell-per-spot platforms (Xenium / MERFISH) use spatial-annotate. For tissue-region detection (no reference needed) use spatial-domains.

Inputs & Outputs

InputFormatRequired
Spatial AnnData.h5ad with obsm["spatial"]yes (unless --demo)
scRNA reference.h5ad with cell-type labels in obs (--reference)required for all real-data methods
OutputPathNotes
Annotated spatial AnnDataprocessed.h5adadds obsm[f"deconvolution_{method}"] (spots × cell-types; spatial_deconv.py:592) and per-method obs columns prefixed deconv_{method}_ (e.g., deconv_flashdeconv_dominant_cell_type, deconv_flashdeconv_dominant_proportion; :692-697)
Proportions tabletables/proportions.csvwide: rows = spots, cols = cell types
Per-spot metricstables/deconv_spot_metrics.csvdominant celltype + diversity per spot
Dominant per-celltypetables/dominant_celltype_counts.csvalways
Diversity indextables/celltype_diversity.csvShannon-style per spot
Cross-method auxiliariestables/dominant_celltype.csv, tables/mean_proportions.csvalways
Reportreport.md + result.jsonalways

Flow

  1. Load spatial AnnData + reference (--reference .h5ad with cell-type labels). For flashdeconv reference is optional (uses internal heuristic).
  2. parser.error validates --input / --reference / numeric flags (lines :300-350).
  3. Dispatch to method; method-specific kwargs from METHOD_PARAM_DEFAULTS.
  4. Build proportions matrix; compute per-spot dominant cell-type + Shannon diversity.
  5. Save processed.h5ad (with obsm["proportions"]), tables, figures, report.md, result.json.

Gotchas

  • All input + parameter validation goes through parser.error (exit code 2). spatial_deconv.py:300 for missing --input; :302 for missing input path; :306 for missing --reference on methods that need one; :308 for missing reference path; :335 and :338-350 for per-method numeric flag validation. Wrappers expecting ValueError need to catch exit-2.
  • --reference is required for almost every method (only flashdeconv can run without it). spatial_deconv.py:306 raises parser.error(f"--reference is required for method '{args.method}'") for the others. The reference must have cell-type labels in obs (key auto-resolved from common names).
  • Stored deconvolution-matrix lookup raises post-load. spatial_deconv.py:594 raises ValueError(f"Stored deconvolution matrix '<prop_key>' not found in adata.obsm") when re-rendering an already-deconvolved AnnData and the obsm key is missing. Used by the replot workflow.
  • obsm["spatial"] ↔ obsm["X_spatial"] sync at :534-536. Same dual-key pattern as spatial-domains — both keys exist after a run.
  • --cell2location-detection-alpha must be > 0. spatial_deconv.py:340 enforces. The cell2location default (typically 200) is a regularisation strength — lower values mean less spatial smoothing.
  • --destvi-dropout-rate is in [0, 1), not [0, 1]. spatial_deconv.py:342 enforces strict-less-than-1. dropout=1 would zero out everything.
  • R-backed methods (rctd, card) need a working R env. Both rely on R packages (spacexr for RCTD, CARD for CARD). Missing R deps surface as ImportError at runtime, not at preflight.

Key CLI

# Demo (synthetic; flashdeconv default)
python omicsclaw.py run spatial-deconv --demo --output /tmp/spatial_deconv_demo

# FlashDeconv (CPU-only, fastest)
python omicsclaw.py run spatial-deconv \
  --input visium.h5ad --reference scrna_atlas.h5ad --output results/ \
  --method flashdeconv

# Cell2location (Bayesian, GPU)
python omicsclaw.py run spatial-deconv \
  --input visium.h5ad --reference scrna_atlas.h5ad --output results/ \
  --method cell2location --cell2location-n-epochs 30000 \
  --cell2location-n-cells-per-spot 8 --cell2location-detection-alpha 200

# RCTD (R-backed)
python omicsclaw.py run spatial-deconv \
  --input visium.h5ad --reference scrna_atlas.h5ad --output results/ \
  --method rctd --rctd-mode full

# Tangram (gradient mapping)
python omicsclaw.py run spatial-deconv \
  --input visium.h5ad --reference scrna_atlas.h5ad --output results/ \
  --method tangram --tangram-n-epochs 1000 --tangram-learning-rate 0.1

# CARD (Conditional Autoregressive R deconv)
python omicsclaw.py run spatial-deconv \
  --input visium.h5ad --reference scrna_atlas.h5ad --output results/ \
  --method card

See also

  • references/parameters.md — every CLI flag, per-method tunables
  • references/methodology.md — when each backend wins; reference-data prep
  • references/output_contract.md — obsm["proportions"] / obs["dominant_celltype"] schema
  • Adjacent skills: spatial-preprocess (upstream — produces the input AnnData), sc-cell-annotation (upstream — labels the scRNA reference passed via --reference), spatial-annotate (parallel — for single-cell-per-spot platforms NOT spot deconvolution), spatial-domains (parallel — finds tissue regions WITHOUT a reference; complementary to deconv), spatial-de (downstream — DE between deconv-defined dominant-celltype groups)