Multi-omic single-cell velocity models epigenome–transcriptome interactions and improves cell fate prediction
Open accessAbstract
Multi-omic single-cell datasets, in which multiple molecular modalities are profiled within the same cell, offer an opportunity to understand the temporal relationship between epigenome and transcriptome. To realize this potential, we developed MultiVelo, a differential equation model of gene expression that extends the RNA velocity framework to incorporate epigenomic data. MultiVelo uses a probabilistic latent variable model to estimate the switch time and rate parameters of chromatin accessibility and gene expression and improves the accuracy of cell fate prediction compared to velocity estimates from RNA only. Application to multi-omic single-cell datasets from brain, skin and blood cells reveals two distinct classes of genes distinguished by whether chromatin closes before or after transcription ceases. We also find four types of cell states: two states in which epigenome and transcriptome are coupled and two distinct decoupled states. Finally, we identify time lags between transcription factor expression and binding site accessibility and between disease-associated SNP accessibility and expression of the linked genes. MultiVelo is available on PyPI, Bioconda and GitHub ( https://github.com/welch-lab/MultiVelo ).
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MultiVelo integrates chromatin accessibility and gene expression to estimate chromatin accessibility switches and gene splicing states.
“These methods can also be extended to model post-transcriptional regulation and predict future cellular states, such as MultiVelo, which integrates chromatin accessibility and gene expression to estimate chromatin accessibility switches and gene splicing states180.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [180]
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- Authors
- Li, C., Virgilio, M. C., Collins, K. L., & Welch, J. D.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Welch, Joshua D.
- Venue
- Nature Biotechnology
- Published
- 2022-10-13
- Volume
- 41
- Issue
- 3
- Pages
- 387-398
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC10246490
- OpenAlex
- W4305013698
- Cited by
- 130
- References
- 78
- Citations by year
- 2026: 37 · 2025: 44 · 2024: 34 · 2023: 13 · 2022: 2
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, other-oa)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (T32GM141746, F31AI155047, T32GM007315, R01AI149669, R01HG010883)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- RNA velocity, chromatin accessibility, differential equation model, cell fate prediction, probabilistic latent variable models, transcription factor binding sites, single-cell multi-omics, gene expression dynamics, disease-associated SNPs
- MeSH terms
- Epigenome, Multiomics, Chromatin, RNA, Single-Cell Analysis, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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