Accurate and fast cell marker gene identification with COSG

Overview

COSG is a cosine similarity-based method for more accurate and scalable marker gene identification.

• COSG is a general method for cell marker gene identification across different data modalities, e.g., scRNA-seq, scATAC-seq, and spatially resolved transcriptome data.
• Marker genes or genomic regions identified by COSG are more indicative and with greater cell-type specificity.
• COSG is ultrafast for large-scale datasets and is capable of identifying marker genes for one million cells in less than two minutes.

The method and benchmarking results are described in Dai et al. (2022).

Additionally, the R version of COSG is available here.

Note I: we released our Python toolkit, PIASO, in which some methods were built upon COSG.

Note II: we have also recently released PIASOmarkerDB for beta testing.

Note III: COSG is also available for online analysis via Galaxy platform.

Documentation

COSG documentation.

Installation

Stable version (PyPI):

pip install cosg

Stable version (bioconda):

conda install -c conda-forge -c bioconda cosg

Development version:

pip install git+https://github.com/genecell/COSG.git

Release notes

Release v1.1.3 (August 24, 2026)

• Fixed: run_cosg_cytome(layer='auto') normalized an already-normalized matrix a second time. auto chose log1p for RNA from a table keyed on the modality alone, without looking at the data. Because cytome.from_anndata stores whatever adata.X held under {modality}_counts — including a log-normalized matrix — any file written from normalized input had log1p applied twice, while the function is documented as equivalent to cosg.cosg(adata). Correlation with the in-memory reference stayed around 0.99 and specificity moved by up to 0.11: small enough to pass a glance, large enough to change which genes rank as markers. auto now probes the stored matrix and, when it is demonstrably not integer, uses the values as given and warns, naming the override. An explicit layer= is obeyed untouched.
• Fixed: the version had two sources of truth. pyproject.toml and cosg/__init__.py each carried a literal, and they agree only until a release bumps one of them. pyproject now declares the version dynamic and reads cosg.__version__.
• Interoperates with cytome 0.3.0. That release stops from_anndata writing a non-integer adata.X to {modality}_counts, so newer files carry {modality}_data (or a name you chose) instead. layer='auto' recognises this: it reads the recorded _anndata_X_layer, uses that matrix, and says which one it picked. Where cytome records matrix_meta.is_integer, that is preferred over probing the values. The minimum cytome version is unchanged at 0.2.3 — this release exists to read older files correctly, and requiring 0.3.0 would help none of them.
• If you have run run_cosg_cytome(layer='auto') on a cytome converted from a normalized AnnData, re-run it. Runs on raw-count files are unaffected, and any run that passed an explicit layer= was always correct.

Release v1.1.2 (August 22, 2026)

• Fixed: cosg.cosg(adata) raised ImportError on a default install. The cytome Dataset alias lookup was not guarded like the first one, so a missing optional cytome dependency produced an error instead of the documented empty-tuple fallback. Plain AnnData no longer requires cytome to be installed.
• Fixed: plt.cm.get_cmap, removed in matplotlib 3.9, replaced with plt.get_cmap.

Release v1.1.1 (August 15, 2026)

• Fixed the PyPI project page, which showed a single sentence instead of this README. The readme field pointed at an inline string rather than at README.rst, so the long description was never packaged. Code is identical to v1.1.0.

Release v1.1.0 (August 12, 2026)

• Added a streaming backend for .cytome datasets: marker detection reads the file in chunks, so peak memory does not scale with the number of cells.
• The cytome streaming backend is an optional extra, on the same reasoning as scanpy above: pip install 'cosg[cytome]'. Calling cosg.cosg() on a .cytome path without it raises an error naming the extra rather than failing obscurely.
• The default streaming path no longer needs PIASO. layer='log1p' (the RNA default) is computed by COSG itself and gives identical numbers to the implementation it replaced. Only layer='infog' and layer='tfidf' need PIASO, since those are PIASO normalizations; the error naming it now gives the correct install command, pip install piaso-tools.
• Added a GPU path (CuPy), selected with device='cpu' | 'gpu' | 'auto' on both the in-memory and streaming paths.
• cosg.cosg() is now a single polymorphic entry point. It dispatches on its first argument:
  • an AnnData takes the in-memory path and writes adata.uns[key_added]
  • a str or pathlib.Path to a .cytome file takes the streaming path and returns a dict
  • an open CytomeDataset (from cytome.open()) also takes the streaming path; the caller keeps ownership of it and it is not closed
• Extended batch_key to the streaming, GPU and feature-batched paths.
• Added output_format for the streaming path: 'dict', 'long' or 'dense'.
• Added cosg.__version__, which previously raised AttributeError.
• scanpy is now an optional extra rather than a required dependency. Only plotMarkerDotplot uses it, so a plain pip install cosg is ~60 MB and 9 packages lighter. Install pip install 'cosg[dotplot]' to keep that function; calling it without scanpy raises an error naming the extra. Cell-type ordering that previously used scanpy.tl.dendrogram is now computed internally and reproduces it exactly.
• The streaming default layer is resolved from the modality: RNA/GA to log1p, ATAC/tiles to tfidf.
• Behaviour change: remove_lowly_expressed now defaults to True on the AnnData path, matching the streaming variant. Pass remove_lowly_expressed=False to restore the previous behaviour.
• Behaviour change: IQR normalisation is computed over all values per group, matching iqrLogNormalize.

Release v1.0.4 (March 5, 2026)

• Added plotMarkerStream for visualising marker gene specificity as a streamgraph.
• Added expressed_min_num_cells_in_target_group (default 3), which floors the expression threshold at max(n_cells * expressed_pct, 3) so small clusters do not get an overly permissive cutoff.
• Added input validation for groupby, groups, groups combined with batch_key, and n_genes_user.

Release v1.0.3 (March 11, 2025)

• Fixed the incompatibility with multiple index columns of adata.uns['cosg']['COSG'] in adata.write function
• Enhanced plotMarkerDendrogram function with several new capabilities:
  • Implemented support for customized cell type-gene pairs
  • Added color control for nodes and edges
  • Added cell type filtering functionality
  • Integrated support for curved edges in visualization

Release v1.0.2 (March 5, 2025)

• Added plotMarkerDotplot and plotMarkerDendrogram for enhanced marker gene visualization.
• Introduced support for batch_key to compute cosine similarities separately across different batches.
• Enabled calculation of normalized COSG scores for comparing gene expression specificity across cell types or datasets.
• Resolved a SciPy version deprecation issue related to .A attribute usage.
• Fixed a DataFrame manipulation warning.
• Added verbosity control, allowing users to adjust log output levels.

Release v1.0.1 (June 15, 2021)

• First release in PyPI.

Example

Run COSG:

import cosg
n_genes=30
groupby='CellTypes'
cosg.cosg(
   adata,
   key_added='cosg',
   # use_raw=False, layer='log1p', ## e.g., if you want to use the log1p layer in adata
   mu=100,
   expressed_pct=0.1,
   remove_lowly_expressed=True,
   n_genes_user=n_genes,
   groupby=groupby
)

Draw the dot plot:

cosg.plotMarkerDotplot(
    adata,
    groupby=groupby,
    top_n_genes=3,
    key_cosg='cosg',
    use_rep='X_pca', ## Change use_rep to the cell embeddings key you'd like to use
    swap_axes=False,
    standard_scale='var',
    cmap='Spectral_r',
    # save='test.pdf'
)

Output the marker list as pandas dataframe:

marker_gene=pd.DataFrame(adata.uns['cosg']['names'])
marker_gene.head()

You could also check the COSG scores:

marker_gene_scores=pd.DataFrame(adata.uns['cosg']['scores'])
marker_gene_scores.head()

Question

For questions about the code and tutorial, please contact Min Dai, dai@broadinstitute.org.

Citation

If COSG is useful for your research, please consider citing Dai et al. (2022).

Execution modes

COSG runs the same algorithm in several modes, selected by the available hardware:

Mode	Speedup	Memory	Requirements
CPU chunked	1.8x	~19 GB	Default, any system
CPU legacy	1.0x	~38 GB	cpu_chunk_size=0
GPU monolithic	6.7x	15 GB VRAM	24+ GB GPU
GPU chunked	4.7x	0.9 GB	Any GPU (4+ GB)

Benchmarked on Allen Institute Human Neocortex (148K cells x 30K genes).

All four modes read an in-memory AnnData, so peak memory still scales with the size of the object. To keep memory bounded by the chunk size instead, read straight from a file — see Cytome datasets.

COSG does not modify the input adata.X. It is safe to call cosg.cosg() without copying adata first.

Optional extras

pip install cosg covers marker detection, plotMarkerDendrogram and plotMarkerStream. Two features need extras:

pip install 'cosg[dotplot]'   # plotMarkerDotplot (wraps scanpy.pl.dotplot)
pip install 'cosg[gpu]'       # the CuPy GPU path, device='gpu'

scanpy was a hard dependency through 1.0.4. It is now optional because only plotMarkerDotplot uses it, and requiring it cost every install ~60 MB and 9 packages (statsmodels, seaborn, umap-learn, ...) for one plotting function. Calling plotMarkerDotplot without it raises an error naming the extra.

Cytome datasets

Marker genes can be computed directly from a .cytome file, without loading the matrix into memory and without going through AnnData:

pip install cytome

import cosg

markers = cosg.cosg(
    "atlas.cytome",
    groupby="cell_type",
    modality="RNA",
    layer="counts",
    n_genes_user=50,
)

cosg.cosg() dispatches on its first argument. An AnnData takes the in-memory path and writes adata.uns[key_added]; a path to a .cytome file takes the streaming path, reads the file in chunks and returns a dict of names, scores and groups_order. Peak memory is set by the chunk size, not by the number of cells.

layer= names a matrix stored in the file. Omit it and the default is resolved from the modality — RNA/GA to log1p, ATAC/tiles to tfidf — which normalizes on the fly and therefore also needs pip install piaso. Pass a stored layer, as above, to run with cosg and cytome alone. output_format= selects dict, long or dense.

cytome is a single-file, SQLite-backed format that holds matrices, cell and feature metadata, embeddings and genomic fragments together: https://github.com/genecell/cytome