Omicverse Single Cell Cellvote Consensus

OmicVerse Single-Cell — CellVote Multi-Annotator Consensus

Goal

Take an annotated AnnData that already has labels from two or more annotators (e.g. obs['scsa_annotation'], obs['gpt_celltype'], obs['gbi_celltype']) and produce a per-cluster consensus label in obs['CellVote_celltype']. The class wraps the upstream annotators (so you can populate them via the same object) and arbitrates by either calling an LLM with the per-cluster candidate set + the cluster's marker genes (online; requires API key) or running a deterministic local-majority vote on lower-cased candidates (offline; tutorial-canonical demo).

CellVote is OmicVerse's own consensus layer; it's distinct from single-popv-annotation (POPV is a separate Bayesian voting tool from a different group). CellVote can include POPV as one of its inputs but is not a wrapper for POPV.

Quick Workflow

1. Ensure each candidate annotator's labels are populated in obs columns (e.g. scsa_annotation, gpt_celltype, gbi_celltype). Either run the annotators yourself (see Branch Selection for the pre-baked cv.scsa_anno() / cv.gpt_anno() / cv.gbi_anno() etc.) or import labels from elsewhere.
2. Compute cluster-level marker genes — marker_dict[cluster_id] = [top_genes...]. CellVote uses these to give the LLM (or the local arbitrator) biological context per cluster.
3. Construct: cv = CellVote(adata). Stores the AnnData reference; doesn't run anything yet.
4. Vote (online, LLM): final_map = cv.vote(clusters_key='leiden', cluster_markers=marker_dict, celltype_keys=['scsa_annotation', 'gpt_celltype', 'gbi_celltype'], species='human', organization='PBMC', provider='openai', model='gpt-4o-mini', api_key='sk-...', result_key='CellVote_celltype'). Calls the LLM once per cluster with the candidate labels + markers + species/organization context; LLM returns a single arbitrated label. Result lands in adata.obs['CellVote_celltype'].
5. Vote (offline, local majority): monkey-patch omicverse.single._cellvote.get_cluster_celltype = local_fn before calling cv.vote(...). The local function takes the same (cluster_celltypes, cluster_markers, species, organization, model, base_url, provider, api_key) signature and returns a dict mapping cluster → consensus label. The tutorial provides a one-line pd.Series.value_counts().idxmax() implementation that's deterministic and free.
6. Inspect: compare obs[['leiden', 'scsa_annotation', 'gpt_celltype', 'gbi_celltype', 'CellVote_celltype']].head() and the per-cluster summary obs.groupby('leiden')[annot_cols].agg(lambda s: s.value_counts().index[0]).

Interface Summary

ov.single.CellVote(adata: AnnData) -> None
# Constructor; stores adata reference.

Per-annotator runners (each populates a different obs column):

• cv.scsa_anno() — runs the SCSA pipeline; writes obs['scsa_annotation']. (Documented in single-cell-annotation skill.)
• cv.gpt_anno() — gpt4celltype-style LLM annotation; writes obs['gpt_celltype'].
• cv.gbi_anno() — GPTBioInsightor; writes obs['gbi_celltype'].
• cv.scMulan_anno() — scMulan large-language model; writes the corresponding column.
• cv.popv_anno(ref_adata, ref_labels_key, ref_batch_key, query_batch_key=None, cl_obo_folder=None, save_path='tmp', prediction_mode='fast', methods=None, methods_kwargs=None) — PopV consensus from a reference; writes its own column. (Use single-popv-annotation skill for stand-alone PopV.)

Consensus voting:

cv.vote(
    clusters_key: str = None,
    cluster_markers: dict[str, list[str]] = None,
    celltype_keys: list[str] = [],
    model: str = 'gpt-3.5-turbo',
    base_url: str = None,
    species: str = 'human',
    organization: str = 'stomach',
    provider: str = 'openai',
    result_key: str = 'CellVote_celltype',
) -> dict[cluster_id, label]
# Writes adata.obs[result_key]; returns the cluster → label dict.

Offline arbitrator (monkey-patch pattern):

import omicverse.single._cellvote as cvmod

def local_majority_arbitration(cluster_celltypes, cluster_markers,
                               species, organization, model, base_url,
                               provider, api_key=None, **kwargs):
    out = {}
    for cl, cand in cluster_celltypes.items():
        if not cand:
            out[cl] = 'unknown'
        else:
            s = pd.Series(cand).str.lower()
            out[cl] = s.value_counts().idxmax()
    return out

cvmod.get_cluster_celltype = local_majority_arbitration
# Then cv.vote(...) uses the patched function.

Boundary

Inside scope:

• Multi-annotator consensus arbitration (LLM or local-majority).
• The pre-baked annotator runners (scsa_anno, gpt_anno, gbi_anno, scMulan_anno, popv_anno).
• Custom arbitration via the monkey-patch hook.

Outside scope — separate skill:

• Running individual annotators stand-alone — see single-cell-annotation (CellTypist / SCSA / gpt4celltype) and single-popv-annotation (POPV).
• Cell Ontology mapping of the consensus labels — see omicverse-single-cell-cellmatch-ontology.
• MetaTiME tumour-microenvironment annotation — see omicverse-single-cell-metatime-annotation.
• Cross-modality label transfer — see cross-modal-celltype-transfer.

Branch Selection

Online vs offline arbitration

• Online (LLM): pass provider='openai' (or 'custom_openai' with base_url) + api_key. The LLM sees the per-cluster candidate labels AND the marker genes AND the species / organization context — typically produces a more biologically informed consensus, especially when annotators disagree. Costs ~$0.001 per cluster on gpt-4o-mini; total run ~$0.01 for a 20-cluster cohort.
• Offline (local majority): monkey-patch cvmod.get_cluster_celltype before voting. Deterministic, free, no network. Tutorial-recommended for CI / reproducibility.
• Hybrid pattern: run offline first to get a deterministic baseline; run online on a copy of the AnnData; compare. Disagreements highlight where biology is ambiguous.

Annotator selection (celltype_keys)

• Two annotators: still works — but ties are resolved alphabetically in local-majority mode (suboptimal). Add a third for tie-breaking.
• Three annotators (canonical): SCSA + gpt4celltype + GPTBioInsightor. Tutorial default.
• More annotators: monotonically improves consensus quality but increases LLM tokens and runtime.

provider and model

• provider='openai' + model='gpt-4o-mini' (tutorial demo): cheap, fast, accurate enough for consensus. Pass api_key=... from env.
• provider='openai' + model='gpt-4o-2024-11-20': more expensive, more accurate on edge cases.
• provider='custom_openai' + base_url='https://...': any OpenAI-compatible endpoint (Azure, Ollama, vLLM, OhMyGPT).

species / organization

• Required for the LLM context. species='human', organization='PBMC' for the tutorial. Wrong values → LLM hallucinates non-existent cell types.
• For non-typical organisms, organization can be free-text (e.g. 'mouse spleen post-LPS') — the LLM uses it as prompt context.

cluster_markers source

• Pass cluster-level top markers (typically 5–10 per cluster). Build from sc.tl.rank_genes_groups results, or from your own DEG analysis.
• For LLM arbitration: more markers (5–10) help the LLM disambiguate; fewer (2–3) underdetermine the cluster.
• For local-majority: cluster_markers is not used (the arbitration is purely candidate-frequency); pass anyway since the API requires it.

Annotator pre-population

• If you haven't run annotators yet: use cv.scsa_anno() etc. to populate them via the same cv object.
• If labels come from elsewhere (a previous run, a collaborator's output): just write them into obs[<keyname>] manually before voting.
• Heterogeneous label vocabularies (e.g. one annotator says 'CD8 T', another says 'CD8+ T cell'): standardise first with the cellmatch skill, then vote. Otherwise the local-majority arbitrator counts these as different votes.

Input Contract

• AnnData with obs[clusters_key] populated (typically 'leiden').
• For each key in celltype_keys: obs[key] populated with cell-type strings. Empty / NaN values get treated as 'unknown' candidate.
• cluster_markers: dict[cluster_id, list[gene_str]]. Cluster IDs must match the unique values in obs[clusters_key] (string types).
• For online voting: outbound HTTPS to OpenAI (or compatible); valid api_key. ~10s per cluster.
• For offline voting: monkey-patch in place before cv.vote(...).

Minimal Execution Patterns

import os
import numpy as np
import pandas as pd
import anndata as ad
import scanpy as sc
import omicverse as ov
from omicverse.single import CellVote

# 1) Load PBMC3k and preprocess
adata = sc.datasets.pbmc3k_processed()
sc.tl.rank_genes_groups(adata, 'leiden', method='wilcoxon')

# Build marker_dict for the LLM context
marker_dict = {
    cluster: list(adata.uns['rank_genes_groups']['names'][cluster][:5])
    for cluster in adata.obs['leiden'].cat.categories
}

# 2) Populate three annotator columns (here: simulated; in practice, run the annotators)
adata.obs['scsa_annotation'] = ...     # from cv.scsa_anno() or external
adata.obs['gpt_celltype']    = ...     # from cv.gpt_anno() or external
adata.obs['gbi_celltype']    = ...     # from cv.gbi_anno() or external

# 3) Online consensus (requires API key)
cv = CellVote(adata)
final_map = cv.vote(
    clusters_key='leiden',
    cluster_markers=marker_dict,
    celltype_keys=['scsa_annotation', 'gpt_celltype', 'gbi_celltype'],
    species='human',
    organization='PBMC',
    provider='openai',
    model='gpt-4o-mini',
    # api_key='sk-...',
)
# adata.obs['CellVote_celltype'] populated; final_map is the cluster -> label dict

# 4) Offline local-majority arbitration (deterministic, free)
import omicverse.single._cellvote as cvmod

def local_majority_arbitration(cluster_celltypes, cluster_markers,
                               species, organization, model, base_url,
                               provider, api_key=None, **kwargs):
    out = {}
    for cl, cand in cluster_celltypes.items():
        if not cand:
            out[cl] = 'unknown'
        else:
            s = pd.Series(cand).str.lower()
            out[cl] = s.value_counts().idxmax()
    return out

cvmod.get_cluster_celltype = local_majority_arbitration

cv = CellVote(adata)
final_map_offline = cv.vote(
    clusters_key='leiden',
    cluster_markers=marker_dict,
    celltype_keys=['scsa_annotation', 'gpt_celltype', 'gbi_celltype'],
    species='human', organization='PBMC',
    provider='openai', model='gpt-4o-mini',  # ignored by the patched function
)
print(adata.obs[['leiden', 'scsa_annotation', 'gpt_celltype',
                 'gbi_celltype', 'CellVote_celltype']].head())

# 5) Per-cluster summary table
cols = ['leiden', 'scsa_annotation', 'gpt_celltype',
        'gbi_celltype', 'CellVote_celltype']
summary = (adata.obs
              .groupby('leiden')[cols[1:]]
              .agg(lambda s: s.value_counts().index[0]))
print(summary)

Validation

• After cv.vote(...): adata.obs['CellVote_celltype'] populated with no NaN cells (clusters with no candidate labels become 'unknown').
• Compare cv.vote(...) keys against obs[clusters_key].unique() — every cluster should be in the returned dict.
• Disagreement diagnostic: for each cluster, count candidate labels — if all 3 annotators agree, consensus is trivially that label. Where they disagree, the LLM (online) typically picks the most marker-supported one; the local-majority (offline) just picks the most-frequent.
• LLM arbitrator failures: if 'unknown' appears in many CellVote_celltype outputs, the LLM rejected the candidates (often because the cluster's marker genes don't match any of the candidate cell types). Inspect cluster_markers[cluster] and the candidate set manually.
• Heterogeneous vocabulary: if 'CD8 T' and 'CD8+ T cell' co-exist, local-majority sees them as different votes and may pick the third (different) annotator's answer. Standardise via the cellmatch skill before voting.
• For online runs: log the LLM cost per call (gpt-4o-mini is ~$0.001/cluster); total cost is n_clusters × 0.001 USD.

Resource Map

• See reference.md for compact copy-paste snippets per mode.
• See references/source-grounding.md for verified CellVote constructor + method signatures and the LLM-arbitrator dispatch path.
• For individual annotators (CellTypist / SCSA / gpt4celltype), see existing single-cell-annotation skill.
• For POPV (a different consensus tool), see existing single-popv-annotation skill.
• For Cell Ontology mapping of CellVote outputs (label standardisation across cohorts), see omicverse-single-cell-cellmatch-ontology.

Examples

• "Build a consensus label from scsa_annotation + gpt_celltype + gbi_celltype on PBMC3k via local-majority arbitration (offline)."
• "Run online CellVote with gpt-4o-mini on a 20-cluster cohort and report the cost."
• "Diagnose why CellVote keeps returning 'unknown' for cluster 5 — likely the markers don't match any annotator's candidate."
• "Run all three annotators (cv.scsa_anno(), cv.gpt_anno(), cv.gbi_anno()), then cv.vote(...) for a one-shot consensus pipeline."

References

• Tutorial notebook: t_cellvote_pbmc3k.ipynb — PBMC3k offline-and-online consensus.
• Live API verified — see references/source-grounding.md.