scCellFie 0.5.0
A tool for inferring metabolic activities from single-cell and spatial transcriptomics

|PYPI| |Issues| |Codecov| |Downloads| |License|

.. |PYPI| image:: https://badge.fury.io/py/sccellfie.svg
   :target: https://pypi.org/project/sccellfie/

.. |Issues| image:: https://github.com/earmingol/scCellFie/actions/workflows/tests.yml/badge.svg
   :alt: test-sccellfie

.. |Codecov| image:: https://codecov.io/gh/earmingol/scCellFie/graph/badge.svg?token=22NENAKNKI
   :target: https://codecov.io/gh/earmingol/scCellFie

.. |Downloads| image:: https://pepy.tech/badge/sccellfie/month
   :target: https://pepy.tech/project/sccellfie

.. |License| image:: https://img.shields.io/badge/License-MIT-yellow.svg
   :target: https://opensource.org/licenses/MIT
   :alt: License: MIT


Metabolic activity from single-cell and spatial transcriptomics with scCellFie
------------------------------------------------------------------------------

scCellFie is a Python-based tool for analyzing metabolic activity at different resolutions, developed at the `Vento Lab <https://ventolab.org/>`_. It efficiently processes both
single-cell and spatial data to predict metabolic task activities. While its prediction strategy is inspired by
`CellFie <https://github.com/LewisLabUCSD/CellFie>`_, a tool from the `Lewis Lab <https://lewislab.ucsd.edu/>`_ originally developed in MATLAB for bulk and small single-cell datasets,
scCellFie includes a series of improvements and new analyses, such as marker selection, differential analysis, and
cell-cell communication inference.


.. image:: https://github.com/earmingol/scCellFie/blob/main/scCellFie-analysis.png?raw=true
   :alt: Logo
   :width: 500
   :height: 590
   :align: center

Features
--------

- **Single cell and spatial data analysis:** Inference of metabolic
  activity per single cell or spatial spot.

- **Speed:** Runs fast and memory efficiently, scaling up to large datasets. ~100k single cells can be analyzed in ~8 min.

- **Downstream analyses:** From marker selection of relevant metabolic tasks to integration with
  inference of cell-cell communication.

- **User-friendly:** Python-based for easier use and integration into existing workflows, including Jupyter Notebooks.

- **Scanpy compatibility:** Fully integrated with Scanpy, the popular single-cell
  analysis toolkit.

- **Organisms:** Metabolic database and analysis available for human and mouse.

Documentation and Tutorials
---------------------------

- For detailed documentation and tutorials, visit the `scCellFie documentation <https://sccellfie.readthedocs.io>`_.

- For visualizing a summarized version of the results, visit the `scCellFie Metabolic Task Visualizer <https://www.sccellfie.org/>`_.

Installation
------------

To create a new conda environment (optional)::

    # Create a new conda environment
    conda create -n sccellfie -y python=3.10

    # Activate the environment
    conda activate sccellfie

To install scCellFie, use pip::

    pip install sccellfie

Quick Start
-----------

A quick example of how to use scCellFie with a single-cell dataset to infer metabolic activities and export them::

        import sccellfie
        import scanpy as sc

        # Load the dataset
        adata = sc.read(filename='./data/HECA-Subset.h5ad',
                        backup_url='https://zenodo.org/records/15072628/files/HECA-Subset.h5ad')

        # Run one-command scCellFie pipeline
        results = sccellfie.run_sccellfie_pipeline(adata,
                                                   organism='human',
                                                   sccellfie_data_folder=None,
                                                   n_counts_col='n_counts',
                                                   process_by_group=False,
                                                   groupby=None,
                                                   neighbors_key='neighbors',
                                                   n_neighbors=10,
                                                   batch_key='sample',
                                                   threshold_key='sccellfie_threshold',
                                                   smooth_cells=True,
                                                   alpha=0.33,
                                                   chunk_size=5000,
                                                   disable_pbar=False,
                                                   save_folder=None,
                                                   save_filename=None
                                                  )

        # Save adata objects containing single-cell/spatial predictions
        sccellfie.io.save_adata(adata=results['adata'],
                                output_directory='/folder/path/',
                                filename='sccellfie_results'
                                )

        # Summarize results in a cell-group level for the Metabolic Task Visualizer
        report = sccellfie.reports.generate_report_from_adata(results['adata'].metabolic_tasks,
                                                              group_by=cell_group,
                                                              tissue_column='condition',
                                                              feature_name='metabolic_task'
                                                              )

        # Export files to a specific folder.
        sccellfie.io.save_result_summary(results_dict=report, output_directory='/folder/path/')

        # Melted.csv and Min_max.csv are input files for the Metabolic Task Visualizer

To access metabolic activities, we need to inspect ``results['adata']``:

- The processed single-cell data is located in the AnnData object ``results['adata']``.
- The reaction activities for each cell are located in the AnnData object ``results['adata'].reactions``.
- The metabolic task activities for each cell are located in the AnnData object ``results['adata'].metabolic_tasks``.

In particular:

- ``results['adata']``: contains gene expression in ``.X``.
- ``results['adata'].layers['gene_scores']``: contains gene scores as in the original CellFie paper.
- ``results['adata'].uns['Rxn-Max-Genes']``: contains determinant genes for each reaction per cell.
- ``results['adata'].reactions``: contains reaction scores in ``.X`` so every scanpy function can be used on this object to visualize or compare values.
- ``results['adata'].metabolic_tasks``: contains metabolic task scores in ``.X`` so every scanpy function can be used on this object to visualize or compare values.

Other keys in the ``results`` dictionary are associated with the scCellFie database and are already filtered for the elements present
in the dataset (``'gpr_rules'``, ``'task_by_gene'``, ``'rxn_by_gene'``, ``'task_by_rxn'``, ``'rxn_info'``, ``'task_info'``, ``'thresholds'``, ``'organism'``).

How to Cite
-----------

Please consider citing our work if you find scCellFie useful:

- **Atlas-scale metabolic activities inferred from single-cell and spatial transcriptomics**.
  *bioRxiv, 2025*. https://doi.org/10.1101/2025.05.09.653038

Acknowledgments
---------------

This tool is inspired by the original `CellFie tool <https://github.com/LewisLabUCSD/CellFie>`_ developed by
the `Lewis Lab <https://lewislab.ucsd.edu/>`_. Please consider citing their work if you find our tool useful:

- **Model-based assessment of mammalian cell metabolic functionalities using omics data**.
  *Cell Reports Methods, 2021*. https://doi.org/10.1016/j.crmeth.2021.100040

- **ImmCellFie: A user-friendly web-based platform to infer metabolic function from omics data**.
  *STAR Protocols, 2023*. https://doi.org/10.1016/j.xpro.2023.102069

- **Inferring secretory and metabolic pathway activity from omic data with secCellFie**.
  *Metabolic Engineering, 2024*. https://doi.org/10.1016/j.ymben.2023.12.006

Contributing
------------
We welcome contributions! Feel free to add requests in the issues section or directly contribute with a pull request.