Published December 2024 | Published
Journal Article Open

Biophysical model for joint analysis of chromatin and RNA sequencing data

  • 1. ROR icon California Institute of Technology

Abstract

The assay for transposase-accessible chromatin using sequencing (ATAC-seq) can be used to identify open chromatin regions, providing complementary information to RNA-seq which measures gene expression by sequencing. Single-cell multiome methods offer the possibility of measuring both modalities simultaneously in cells, raising the question of how to analyze them jointly, and also the extent to which the information they provide is better than unregistered data, where single-cell ATAC-seq and single-cell RNA-seq are performed on the same sample, but on different cells. We propose and motivate a biophysical model for chromatin dynamics and subsequent transcription that can be used to parametrize multiome data, and use it to assess the benefits of multiome data over unregistered single-cell RNA-seq and single-cell ATAC-seq. We also show that our model provides a biophysically grounded approach to the integration of chromatin accessibility data with other modalitie, and apply the model to single-cell ATAC-seq data.

Copyright and License

©2024 American Physical Society

Acknowledgement

We thank C. Trimble for a generous gift to Caltech's CI2 that partially funded C.F. Thanks to S. Booeshaghi and D. Sullivan for help with snATAK used in preprocessing the single-cell RNA-seq and ATAC-seq data, to T. Chari and M. Carilli for helpful feedback on the paper, and to M. Fang for feedback on the paper in addition to many helpful discussions.

Data Availability

Scripts implementing these analyses and simulations and reproducing Figs. 2–5 are available at https://github.com/pachterlab/FGP_2023.

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Created:
March 1, 2025
Modified:
March 1, 2025