scvi-tools — scVI / scANVI

scvi-tools (Gayoso et al. 2022, github.com/scverse/scvi-tools, BSD-3-Clause) wraps a family of deep generative models for single-cell omics. The scRNA-seq core is scVI (unsupervised batch-corrected latent embedding) and scANVI (scVI + a classifier head for semi-supervised cell-type label transfer). Both expect raw integer UMI counts and emit a low-dimensional X_scVI / X_scANVI that drops into the scanpy neighbors → leiden → umap pipeline.

How to run

scVI — batch-corrected latent space

python
import scanpy as sc
import scvi

adata = sc.read_h5ad("dataset.h5ad")
adata.layers["counts"] = adata.X.copy()          # preserve raw BEFORE any normalize/log1p
sc.pp.normalize_total(adata); sc.pp.log1p(adata) # optional, for HVG / plotting only
sc.pp.highly_variable_genes(adata, n_top_genes=2000, batch_key="batch", subset=True)

scvi.model.SCVI.setup_anndata(adata, layer="counts", batch_key="batch")
model = scvi.model.SCVI(adata, n_latent=30)
model.train(max_epochs=200, early_stopping=True, accelerator="gpu", devices=1)

adata.obsm["X_scVI"] = model.get_latent_representation()
adata.layers["scvi_normalized"] = model.get_normalized_expression(library_size=1e4)

scANVI — label transfer from a partially-annotated reference

python
lvae = scvi.model.SCANVI.from_scvi_model(
    model, labels_key="cell_type", unlabeled_category="Unknown",
)
lvae.train(max_epochs=20, n_samples_per_label=100, accelerator="gpu", devices=1)

adata.obsm["X_scANVI"] = lvae.get_latent_representation()
adata.obs["pred_cell_type"] = lvae.predict()

accelerator="gpu", devices=1 is the PyTorch-Lightning spelling; the legacy use_gpu= kwarg was removed in scvi-tools 1.x and now raises TypeError.

Differential expression

python
de = model.differential_expression(
    groupby="leiden", group1="3",   # group2=None → vs. all other cells
    mode="change", delta=0.25,
)
top = de.sort_values("proba_de", ascending=False).head(50)

For one-vs-rest leave group2 out — "rest" is scanpy's rank_genes_groups convention, not scvi-tools'; here group2 is a literal category name and "rest" would match zero cells.

scvi-tools ≥1.4 defaults to mode="vanilla", whose result columns are exactly:

['proba_m1', 'proba_m2', 'bayes_factor', 'scale1', 'scale2', 'raw_mean1',
 'raw_mean2', 'non_zeros_proportion1', 'non_zeros_proportion2',
 'raw_normalized_mean1', 'raw_normalized_mean2', 'comparison', 'group1',
 'group2']

— no lfc_*, no proba_de, no is_de_fdr_*. Pass mode="change" to get lfc_mean / lfc_median / proba_de / is_de_fdr_0.05. Sort on proba_de (or on bayes_factor if you deliberately stayed in vanilla mode).

Output format

| Key | What | | ------------------------------ | ------------------------------------------------------ | | adata.obsm["X_scVI"] | n_cells × n_latent batch-corrected embedding | | adata.obsm["X_scANVI"] | label-aware embedding (better separates known classes) | | adata.obs["pred_cell_type"] | scANVI predicted label per cell | | adata.layers["scvi_normalized"] | decoded expression, library-size normalized | | DE dataframe | per-gene lfc_* / proba_de (with mode="change") |

Remote compute

A100-class GPU is recommended for more than 50,000 cells. Use a selected and probed ssh:<alias> execution context, then load remote-compute-ssh for the Run lifecycle. Confirm that the remote Python environment imports scvi, scanpy, and anndata; do not assume Wisp provisioned an image.

Write a self-contained project script such as runs/scvi_pipeline.py. The sidecar helper h5ad_safe_obs exists only in the interactive python kernel, so copy its small coercion into the standalone script before writing H5AD. Submit one persisted Run with run_in_context:

json
{
  "context_id": "ssh:gpu-box",
  "title": "scVI and scANVI on 80k cells",
  "command": "source ~/miniforge3/etc/profile.d/conda.sh && conda activate singlecell && python scvi_pipeline.py --input dataset.h5ad --output /home/me/wisp-results/scvi/annotated.h5ad",
  "timeout_secs": 3600,
  "input_paths": ["runs/scvi_pipeline.py", "data/dataset.h5ad"],
  "output_specs": [
    {
      "glob": "ssh://gpu-box/home/me/wisp-results/scvi/annotated.h5ad",
      "kind": "h5ad",
      "residency": "remote"
    }
  ]
}

Replace the context, environment, and absolute output path with probed values. Staged inputs are flattened to basenames. For a large H5AD already on the server, omit it from input_paths and pass its absolute remote path instead. Call monitor_run exactly once when waiting is needed, get_run for one snapshot only, and cancel_run when the user requests cancellation.

Gotchas

| Gotcha | What happens / fix | |---|---| | differential_expression() defaults to mode="vanilla" (scvi-tools ≥1.4) | KeyError: 'lfc_mean' / 'proba_de' when sorting — pass mode="change" to get lfc_*/proba_de/is_de_fdr_*; in vanilla mode sort on bayes_factor. | | adata.obs index/columns are string[pyarrow] (ArrowStringArray) | .write_h5ad() dies with IORegistryError: No method registered for writing <class 'pandas.arrays.ArrowStringArray'> (anndata #2377). Coerce before writing: adata.obs = h5ad_safe_obs(adata.obs) (kernel helper — local kernel only; inline the coercion in remote pipeline.py). .astype(str) alone is not enough — on a pyarrow-backed Index/Series it returns another Arrow-backed array; round-trip through np.asarray(..., dtype=object). anndata.settings.allow_write_nullable_strings = True does not cover Arrow-backed strings. | | use_gpu= kwarg | Removed in 1.x → TypeError: train() got an unexpected keyword argument 'use_gpu'. Use accelerator="gpu", devices=1. | | Log-normalized data fed to setup_anndata | Silent garbage — scVI's NB likelihood needs raw integer counts. Stash counts in adata.layers["counts"] before normalize/log1p and pass layer="counts". |

Troubleshooting

| Symptom | Fix | |---|---| | KeyError: 'lfc_mean' (or 'proba_de', 'is_de_fdr_0.05') on DE result | Add mode="change" to differential_expression(); the default vanilla mode has no LFC columns. | | IORegistryError: No method registered for writing <class 'pandas.arrays.ArrowStringArray'> on .write_h5ad() | adata.obs = h5ad_safe_obs(adata.obs) (and adata.var if needed) before writing. The allow_write_nullable_strings flag does not help here. | | TypeError: ... unexpected keyword argument 'use_gpu' | Replace with accelerator="gpu", devices=1. | | ValueError: ... non-negative integers / NB loss explodes | layer="counts" points at log/float data — restore raw counts. | | MisconfigurationException: No supported gpu backend found | No CUDA visible — drop accelerator/devices to fall back to CPU, or dispatch via Remote compute. | | UnicodeEncodeError: 'ascii' codec can't encode character ... writing a summary / printing | The remote environment has no UTF-8 locale. Open files with encoding="utf-8" and/or call sys.stdout.reconfigure(encoding="utf-8") at script start. | | Run remains active after the conversation ends | This is expected: the persisted Run owns the lifecycle. Use the Runs panel or one get_run snapshot later. |

Next: cluster on X_scVI with scanpy (sc.pp.neighbors(use_rep="X_scVI") → sc.tl.leiden → sc.tl.umap); for spatial deconvolution train cell2location / DestVI / Tangram on the scRNA-seq reference.