Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles
Open accessAbstract
Recently, great progress has been made in single cell genomics and transcriptomics. Here, we present an integrative method, termed single-cell transcriptogenomics (SCTG), in which whole exome sequencing and RNA-seq is performed concurrently on single cells. This methodology enables one to track germline and somatic variants directly from the genome to the transcriptome in individual cells. Mouse embryonic fibroblasts were treated with the powerful mutagen ethylnitrosourea (ENU) and subjected to SCTG. Interestingly, while germline variants were found to be transcribed in an allelically balanced fashion, a significantly different pattern of allelic exclusion was observed for ENU-mutant variants. These results suggest that the adverse effects of induced mutations, in contrast to germline variants, may be mitigated by allelically biased transcription. They also illustrate how SCTG can be instrumental in the direct assessment of phenotypic consequences of genomic variants.
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The first methods developed for integrated multi-omics allow parallel interrogation of the genome and transcriptome of the same cell (G&T-seq, DR-seq and single-cell transcriptogenomics).
“The first methods developed for integrated multi-omics allow parallel interrogation of the genome and transcriptome of the same cell (G&T-seq [79], DR-seq [80] and single-cell transcriptogenomics [81]).”
From Mapping gene regulatory networks from single-cell omics data (2018) · cites this paper as [81]
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Inference of Networks from Large Datasets
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- Authors
- Li, W., Calder, R. B., Mar, J. C., & Vijg, J.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Vijg, Jan
- Venue
- Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 772
- Pages
- 55-62
- ISSN
- 0027-5107 (ISSN-L)
- 1386-1964
- PMC
- PMC4342853
- OpenAlex
- W1971008584
- Cited by
- 34
- References
- 56
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 3
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Mutation research. Fundamental and molecular mechanisms of mutagenesis (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AG038072, P01AG17242, R01AG034421, R21AG030567, R21ES019520, U54RR024346)
- Glenn Foundation for Medical Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- ethylnitrosourea mutagenesis, allelic exclusion, germline mutations, somatic mutations, mouse embryonic fibroblasts, induced mutation
- MeSH terms
- Alkylating Agents, Alleles, Animals, Embryo, Mammalian, Ethylnitrosourea, Fibroblasts, Mutation, Transcription, Genetic, Gene Expression Profiling, Allelic Imbalance, Mice
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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