Related Experiment Video
Updated: Jun 4, 2026
10:03
Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution
Published on: May 12, 2023
Alignment-free integration of single-nucleus ATAC-seq across species with sPYce
Leo Zeitler1, Camille Berthelot2
1Institut Pasteur, Université Paris Cité, CNRS UMR 3525, INSERM U1351, Comparative Functional Genomics group, Paris, France. lzeitler@turing.ac.uk.
Nature Ecology & Evolution
|June 2, 2026
Summary
A new method, sPYce, enables cross-species comparison of gene regulation using single-nucleus assays for transposase-accessible chromatin with sequencing (snATAC-seq). It reveals conserved and species-specific regulatory programs, aiding evolutionary studies.
Area of Science:
- Genomics
- Evolutionary Biology
- Computational Biology
Background:
- Gene regulation differences drive species-specific cellular identities and phenotypes.
- Single-nucleus assays for transposase-accessible chromatin with sequencing (snATAC-seq) identify gene regulatory elements.
- Existing methods for single-cell gene expression data integration are limited for cross-species snATAC-seq analysis.
Purpose of the Study:
- To develop a novel framework for integrating and comparing snATAC-seq data across different species.
- To enable the study of evolutionary divergence in gene regulatory programs.
- To overcome limitations of existing methods in cross-species data integration.
Main Methods:
- Introduced sPYce, an alignment-free method for cross-species snATAC-seq integration.
- Utilized k-mer histograms of regulatory regions based on sequence composition for data anchoring.
- Benchmarked sPYce on datasets spanning over 160 million years of evolution.
Main Results:
- sPYce successfully embeds multi-species snATAC-seq datasets into a shared mathematical space.
- The method uncovers conserved cellular programs while preserving species-specific differences.
- Analysis of mouse and opossum cerebellar development identified regulatory divergence in granule cell differentiation driven by nuclear factor 1.
Conclusions:
- sPYce provides an easy-to-use, alignment-free approach for cross-species snATAC-seq data integration.
- This method opens new avenues for comparative analysis of gene regulatory evolution.
- Facilitates deeper understanding of the genetic basis of species divergence.
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