CZ CELLxGENE Census

Overview

CZ CELLxGENE Census provides programmatic access to 61+ million standardized single-cell RNA-seq observations from human and mouse. It enables population-scale queries by cell type, tissue, disease, and donor metadata, returning expression data as AnnData objects or PyTorch dataloaders for ML workflows.

When to Use

• Querying single-cell expression data across tissues, diseases, or cell types from a curated atlas
• Building reference datasets for cell type classification or marker gene discovery
• Training ML models on large-scale single-cell data (PyTorch integration)
• Comparing gene expression across conditions (e.g., COVID-19 vs healthy) at population scale
• Exploring what single-cell datasets are available for a tissue or disease of interest
• For analyzing your own scRNA-seq data, use scanpy instead
• For manipulating AnnData objects (subsetting, concatenation), use anndata instead

Prerequisites

pip install cellxgene-census
# For ML workflows
pip install cellxgene-census[experimental]

API Rate Limits: Census uses TileDB-SOMA cloud backend. No explicit rate limit, but large queries (>1M cells) should use out-of-core processing (Module 4) to avoid memory exhaustion. Always use context managers for proper resource cleanup.

Quick Start

import cellxgene_census

with cellxgene_census.open_soma() as census:
    # Get B cells from lung
    adata = cellxgene_census.get_anndata(
        census=census,
        organism="Homo sapiens",
        obs_value_filter="cell_type == 'B cell' and tissue_general == 'lung' and is_primary_data == True",
        obs_column_names=["cell_type", "disease", "donor_id"],
    )
    print(f"Retrieved {adata.n_obs} cells × {adata.n_vars} genes")
    # Retrieved ~15000 cells × 60664 genes

Core API

1. Opening and Exploring the Census

Connect to Census and discover available data.

import cellxgene_census

# Open latest stable version (always use context manager)
with cellxgene_census.open_soma() as census:
    # Summary statistics
    summary = census["census_info"]["summary"].read().concat().to_pandas()
    print(f"Total cells: {summary['total_cell_count'][0]:,}")

    # List all datasets
    datasets = census["census_info"]["datasets"].read().concat().to_pandas()
    print(f"Total datasets: {len(datasets)}")
    print(datasets[["dataset_title", "cell_count"]].head())

# Open specific version for reproducibility
with cellxgene_census.open_soma(census_version="2023-07-25") as census:
    # Reproducible analysis code here
    pass

2. Cell Metadata Queries

Query cell-level metadata without downloading expression data.

import cellxgene_census

with cellxgene_census.open_soma() as census:
    # Get unique cell types in brain
    cell_metadata = cellxgene_census.get_obs(
        census,
        "homo_sapiens",
        value_filter="tissue_general == 'brain' and is_primary_data == True",
        column_names=["cell_type", "disease", "assay"]
    )
    print(f"Total brain cells: {len(cell_metadata):,}")
    print(cell_metadata["cell_type"].value_counts().head(10))

    # Gene metadata query
    gene_metadata = cellxgene_census.get_var(
        census,
        "homo_sapiens",
        value_filter="feature_name in ['CD4', 'CD8A', 'FOXP3']",
        column_names=["feature_id", "feature_name", "feature_length"]
    )
    print(gene_metadata)
    # Returns DataFrame with Ensembl IDs, gene symbols, and lengths

3. Expression Data Queries (Small-Medium Scale)

Retrieve expression matrices as AnnData objects for queries returning <100k cells.

import cellxgene_census

with cellxgene_census.open_soma() as census:
    # Query by cell type + tissue + disease
    adata = cellxgene_census.get_anndata(
        census=census,
        organism="Homo sapiens",
        obs_value_filter="cell_type == 'T cell' and disease == 'COVID-19' and is_primary_data == True",
        var_value_filter="feature_name in ['CD4', 'CD8A', 'CD19', 'FOXP3']",
        obs_column_names=["cell_type", "tissue_general", "donor_id"],
    )
    print(f"Shape: {adata.shape}")  # (n_cells, 4)
    print(f"Metadata columns: {list(adata.obs.columns)}")

Filter syntax reference:

• Combine conditions: and, or
• Multiple values: feature_name in ['CD4', 'CD8A']
• Comparison: cell_count > 1000
• Always include is_primary_data == True to avoid duplicate cells

4. Large-Scale Out-of-Core Queries

Stream expression data in chunks for queries exceeding available RAM.

import cellxgene_census
import tiledbsoma as soma

with cellxgene_census.open_soma() as census:
    # Estimate query size first
    metadata = cellxgene_census.get_obs(
        census, "homo_sapiens",
        value_filter="tissue_general == 'brain' and is_primary_data == True",
        column_names=["soma_joinid"]
    )
    n_cells = len(metadata)
    print(f"Query will return {n_cells:,} cells")

    # If >100k cells, use streaming
    query = census["census_data"]["homo_sapiens"].axis_query(
        measurement_name="RNA",
        obs_query=soma.AxisQuery(
            value_filter="tissue_general == 'brain' and is_primary_data == True"
        ),
        var_query=soma.AxisQuery(
            value_filter="feature_name in ['FOXP2', 'TBR1', 'SATB2']"
        )
    )

    # Incremental statistics
    n_obs, total = 0, 0.0
    for batch in query.X("raw").tables():
        values = batch["soma_data"].to_numpy()
        n_obs += len(values)
        total += values.sum()

    print(f"Processed {n_obs:,} non-zero entries, mean={total/n_obs:.4f}")

5. Dataset Presence Matrix

Check which datasets measured specific genes (not all genes are in all datasets).

import cellxgene_census

with cellxgene_census.open_soma() as census:
    presence = cellxgene_census.get_presence_matrix(
        census,
        "homo_sapiens",
        var_value_filter="feature_name in ['CD4', 'CD8A', 'PTPRC']"
    )
    print(f"Presence matrix shape: {presence.shape}")
    # (n_datasets, n_genes) — True if gene measured in dataset

6. PyTorch ML Integration

Train models directly on Census data using the experimental dataloader.

from cellxgene_census.experimental.ml import experiment_dataloader
import cellxgene_census

with cellxgene_census.open_soma() as census:
    dataloader = experiment_dataloader(
        census["census_data"]["homo_sapiens"],
        measurement_name="RNA",
        X_name="raw",
        obs_value_filter="tissue_general == 'liver' and is_primary_data == True",
        obs_column_names=["cell_type"],
        batch_size=128,
        shuffle=True,
    )

    for batch in dataloader:
        X = batch["X"]           # Gene expression tensor
        labels = batch["obs"]    # Cell metadata
        print(f"Batch X shape: {X.shape}, labels: {list(labels.columns)}")
        break  # Show first batch only

Key Concepts

Census Data Model

The Census is organized as a SOMA (Stack of Matrices, Annotated) collection:

census/
├── census_info/
│   ├── summary          # Total cell counts
│   └── datasets         # Dataset metadata
└── census_data/
    ├── homo_sapiens/
    │   └── ms_RNA/
    │       ├── obs      # Cell metadata (61M+ rows)
    │       ├── var      # Gene metadata (~60k rows)
    │       └── X/raw    # Expression matrix (sparse)
    └── mus_musculus/
        └── ...

Key Metadata Fields

Field	Type	Description	Example Values
cell_type	str	Cell Ontology label	"B cell", "neuron", "macrophage"
tissue_general	str	Coarse tissue grouping	"brain", "lung", "blood"
tissue	str	Specific tissue	"prefrontal cortex", "alveolar tissue"
disease	str	Disease state	"normal", "COVID-19", "lung adenocarcinoma"
assay	str	Sequencing assay	"10x 3' v3", "Smart-seq2"
is_primary_data	bool	True = unique cell	Always filter True
donor_id	str	Donor identifier	Used for batch effects

tissue_general vs tissue

Use tissue_general for broad cross-tissue analyses and tissue for specific tissue queries:

# Broad: all immune system cells
obs_value_filter = "tissue_general == 'immune system'"
# Specific: only PBMCs
obs_value_filter = "tissue == 'peripheral blood mononuclear cell'"

Common Workflows

Workflow 1: Cross-Tissue Cell Type Comparison

Goal: Compare macrophage gene expression across tissues.

import cellxgene_census
import scanpy as sc

with cellxgene_census.open_soma() as census:
    adata = cellxgene_census.get_anndata(
        census=census,
        organism="Homo sapiens",
        obs_value_filter=(
            "cell_type == 'macrophage' and "
            "tissue_general in ['lung', 'liver', 'brain'] and "
            "is_primary_data == True"
        ),
        obs_column_names=["cell_type", "tissue_general", "donor_id", "disease"],
    )
    print(f"Macrophages: {adata.n_obs} cells from {adata.obs['tissue_general'].nunique()} tissues")

    # Standard scanpy analysis
    sc.pp.normalize_total(adata, target_sum=1e4)
    sc.pp.log1p(adata)
    sc.pp.highly_variable_genes(adata, n_top_genes=2000)
    sc.pp.pca(adata, n_comps=50)
    sc.pp.neighbors(adata)
    sc.tl.umap(adata)

    # Differential expression across tissues
    sc.tl.rank_genes_groups(adata, groupby="tissue_general")
    sc.pl.umap(adata, color=["tissue_general", "disease"])

Workflow 2: Disease-Associated Gene Expression

Goal: Compare marker gene expression between COVID-19 and healthy controls.

1. Query metadata to identify available cell types in COVID-19 data (Core API module 2)
2. Retrieve expression data for selected cell types and marker genes (Core API module 3)
3. Compute mean expression per cell type per condition
4. Visualize with scanpy dotplot or matrixplot

Key Parameters

Parameter	Function/Endpoint	Default	Range / Options	Effect
organism	get_anndata, get_obs	—	"Homo sapiens", "Mus musculus"	Species selection
census_version	open_soma	latest stable	Date string "YYYY-MM-DD"	Pin to specific data release
obs_value_filter	get_anndata, get_obs	None	SOMA filter expression	Cell-level filtering
var_value_filter	get_anndata, get_var	None	SOMA filter expression	Gene-level filtering
obs_column_names	get_anndata, get_obs	all columns	list of field names	Reduces data transfer
batch_size	experiment_dataloader	128	32–512	PyTorch batch size
shuffle	experiment_dataloader	False	True/False	Randomize training order

Best Practices

1. Always filter is_primary_data == True: Without this filter, duplicate cells across datasets inflate counts and bias analyses.

2. Estimate query size before loading: Call get_obs() with column_names=["soma_joinid"] to count cells before downloading expression data. Use out-of-core processing for >100k cells.

3. Pin census_version for reproducibility: The default "latest stable" changes periodically. Always specify the version for published analyses.

4. Select only needed metadata columns: Passing obs_column_names reduces data transfer and memory usage significantly for large queries.

5. Use tissue_general for cross-tissue analyses: The tissue field has hundreds of specific values; tissue_general provides ~30 coarse groupings suitable for comparative analyses.

6. Anti-pattern — querying all genes when you need a few: Specify var_value_filter to retrieve only genes of interest. Downloading the full ~60k gene matrix for 3 marker genes wastes bandwidth and memory.

Common Recipes

Recipe: Multi-Tissue Dataset Summary

import cellxgene_census
import pandas as pd

with cellxgene_census.open_soma() as census:
    metadata = cellxgene_census.get_obs(
        census, "homo_sapiens",
        value_filter="is_primary_data == True",
        column_names=["tissue_general", "cell_type", "disease"]
    )
    summary = metadata.groupby("tissue_general").agg(
        n_cells=("cell_type", "size"),
        n_cell_types=("cell_type", "nunique"),
        n_diseases=("disease", "nunique"),
    ).sort_values("n_cells", ascending=False)
    print(summary.head(10))

Recipe: Export Census Subset to h5ad

import cellxgene_census

with cellxgene_census.open_soma() as census:
    adata = cellxgene_census.get_anndata(
        census=census,
        organism="Homo sapiens",
        obs_value_filter="tissue_general == 'heart' and is_primary_data == True",
        obs_column_names=["cell_type", "disease", "donor_id", "assay"],
    )
    adata.write_h5ad("heart_cells.h5ad")
    print(f"Saved {adata.n_obs} cells to heart_cells.h5ad")

Troubleshooting

Problem	Cause	Solution
MemoryError on get_anndata()	Query returns too many cells	Check count with get_obs() first; use out-of-core axis_query() for >100k cells
Duplicate cells in results	Missing is_primary_data == True filter	Add is_primary_data == True to all obs_value_filter queries
Gene not found	Wrong gene name or gene not in Census	Check spelling (case-sensitive); try Ensembl ID via feature_id; verify with get_presence_matrix()
ConnectionError / timeout	Census backend temporarily unavailable	Retry after 1-2 minutes; pin a specific census_version for reliability
Version inconsistencies	Using default "latest" across sessions	Always specify census_version in production code
Slow query performance	Downloading all metadata columns	Specify only needed columns via obs_column_names
ImportError: cellxgene_census	Package not installed	pip install cellxgene-census (note the hyphen)

Related Skills

• scanpy-scrna-seq — downstream analysis of Census data (clustering, DEG, visualization)
• anndata-data-structure — manipulating AnnData objects returned by Census queries
• esm-protein-language-model — protein embeddings from sequences; complementary to Census gene expression data

References

• CELLxGENE Census documentation — official API reference
• CELLxGENE Discover — web browser for Census data
• TileDB-SOMA — underlying data access layer
• CZI (2023) "CZ CELLxGENE Discover: A single-cell data platform for scalable exploration, analysis and modeling of aggregated data" — bioRxiv