EpiTrace - Estimating cell age from single-cell ATAC data

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EpiTrace is an R package for estimating cell age from single-cell ATAC-seq data. It takes an approximation approach to infer the relative mitosis (replicative) age – the number of mitosis a cell has undergone. It does so by measuring the total opened reference “clock-like” genomic loci. On these loci, heterogeneity of chromatin accessibility decreases as the cell ages. The chromatin accessibility-based mitosis age inferred by EpiTrace adds a time domain to the single-cell sequencing data. It complements somatic mutation, RNA velocity and stemness predictions to predict the cell evolution trajectory with improved precision and power [Xiao et al., 2024].

EpiTrace’s key applications

  • estimate the mitosis age of single cell or bulk sample.

  • identify age-dependent biological events including shifts in chromatin accessibility, transcription factor activity, and transcriptomic changes.

  • timing developmental and mutational events.

Citing EpiTrace

If you include or rely on EpiTrace when publishing research, please adhere to the following citation guide:

EpiTrace algorithm and the ClockDML

If you use the algorithm and/or ClockDML (clock-like differential methylated loci), including cross-species lift-over clock-like loci generated from the ClockDML, cite

@article {Xiao2024,
    author = {Xiao, Yu and Jin, Wan and Ju, Lingao and Fu, Jie and Wang, Gang and Yu, Mengxue and Chen, Fangjin and Qian, Kaiyu and Wang, Xinghuan and Zhang, Yi},
    title = {Tracking single-cell evolution using clock-like chromatin accessibility loci},
    year = {2024},
    doi = {10.1038/s41587-024-02241-z},
    URL = {https://doi.org/10.1038/s41587-024-02241-z},
    journal = {Nat Biotech}}

G-quadruplex region

If you use the G-quadruplex region for cell/sample age estimation, cite

@article {Jin2024.01.06.574476,
    author = {Wan Jin and Jing Zheng and Yu Xiao and Lingao Ju and Fangjin Chen and Jie Fu and Hui Jiang and Yi Zhang},
    title = {A universal molecular mechanism driving aging},
    elocation-id = {2024.01.06.574476},
    year = {2024},
    doi = {10.1101/2024.01.06.574476},
    publisher = {Cold Spring Harbor Laboratory},
    URL = {https://www.biorxiv.org/content/early/2024/01/06/2024.01.06.574476},
    eprint = {https://www.biorxiv.org/content/early/2024/01/06/2024.01.06.574476.full.pdf},
    journal = {bioRxiv}}

Support

Have a question or would like to start a new discussion? Found a bug or would like to see a feature implemented? Feel free to submit an issue. Your help to improve EpiTrace is highly appreciated.

Planned updates

Tutorial on (1) using G-quadruplex as reference clock-like loci, and (2) timing mutational event during oncogenesis.