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Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements

(2022) NATURE GENETICS. 54(10). p.1564-1571
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Abstract
Single-cell DNA sequencing data are generated from human neurons using primary template-directed amplification and analyzed using SCAN2, an improved genotyping tool. Indels are enriched in neuronal regulatory elements and may be deleterious. Accurate somatic mutation detection from single-cell DNA sequencing is challenging due to amplification-related artifacts. To reduce this artifact burden, an improved amplification technique, primary template-directed amplification (PTA), was recently introduced. We analyzed whole-genome sequencing data from 52 PTA-amplified single neurons using SCAN2, a new genotyper we developed to leverage mutation signatures and allele balance in identifying somatic single-nucleotide variants (SNVs) and small insertions and deletions (indels) in PTA data. Our analysis confirms an increase in nonclonal somatic mutation in single neurons with age, but revises the estimated rate of this accumulation to 16 SNVs per year. We also identify artifacts in other amplification methods. Most importantly, we show that somatic indels increase by at least three per year per neuron and are enriched in functional regions of the genome such as enhancers and promoters. Our data suggest that indels in gene-regulatory elements have a considerable effect on genome integrity in human neurons.
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MLA
Luquette, Lovelace J., et al. “Single-Cell Genome Sequencing of Human Neurons Identifies Somatic Point Mutation and Indel Enrichment in Regulatory Elements.” NATURE GENETICS, vol. 54, no. 10, 2022, pp. 1564–71, doi:10.1038/s41588-022-01180-2.
APA
Luquette, L. J., Miller, M. B., Zhou, Z., Bohrson, C. L., Zhao, Y., Jin, H., … Park, P. J. (2022). Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements. NATURE GENETICS, 54(10), 1564–1571. https://doi.org/10.1038/s41588-022-01180-2
Chicago author-date
Luquette, Lovelace J., Michael B. Miller, Zinan Zhou, Craig L. Bohrson, Yifan Zhao, Hu Jin, Doga Gulhan, et al. 2022. “Single-Cell Genome Sequencing of Human Neurons Identifies Somatic Point Mutation and Indel Enrichment in Regulatory Elements.” NATURE GENETICS 54 (10): 1564–71. https://doi.org/10.1038/s41588-022-01180-2.
Chicago author-date (all authors)
Luquette, Lovelace J., Michael B. Miller, Zinan Zhou, Craig L. Bohrson, Yifan Zhao, Hu Jin, Doga Gulhan, Javier Ganz, Sara Bizzotto, Samantha Kirkham, Tino Hochepied, Claude Libert, Alon Galor, Junho Kim, Michael A. Lodato, I Garaycoechea, Juan, Charles Gawad, Jay West, Christopher A. Walsh, and Peter J. Park. 2022. “Single-Cell Genome Sequencing of Human Neurons Identifies Somatic Point Mutation and Indel Enrichment in Regulatory Elements.” NATURE GENETICS 54 (10): 1564–1571. doi:10.1038/s41588-022-01180-2.
Vancouver
1.
Luquette LJ, Miller MB, Zhou Z, Bohrson CL, Zhao Y, Jin H, et al. Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements. NATURE GENETICS. 2022;54(10):1564–71.
IEEE
[1]
L. J. Luquette et al., “Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements,” NATURE GENETICS, vol. 54, no. 10, pp. 1564–1571, 2022.
@article{8771508,
  abstract     = {{Single-cell DNA sequencing data are generated from human neurons using primary template-directed amplification and analyzed using SCAN2, an improved genotyping tool. Indels are enriched in neuronal regulatory elements and may be deleterious. Accurate somatic mutation detection from single-cell DNA sequencing is challenging due to amplification-related artifacts. To reduce this artifact burden, an improved amplification technique, primary template-directed amplification (PTA), was recently introduced. We analyzed whole-genome sequencing data from 52 PTA-amplified single neurons using SCAN2, a new genotyper we developed to leverage mutation signatures and allele balance in identifying somatic single-nucleotide variants (SNVs) and small insertions and deletions (indels) in PTA data. Our analysis confirms an increase in nonclonal somatic mutation in single neurons with age, but revises the estimated rate of this accumulation to 16 SNVs per year. We also identify artifacts in other amplification methods. Most importantly, we show that somatic indels increase by at least three per year per neuron and are enriched in functional regions of the genome such as enhancers and promoters. Our data suggest that indels in gene-regulatory elements have a considerable effect on genome integrity in human neurons.}},
  author       = {{Luquette, Lovelace J. and Miller, Michael B. and Zhou, Zinan and Bohrson, Craig L. and Zhao, Yifan and Jin, Hu and Gulhan, Doga and Ganz, Javier and Bizzotto, Sara and Kirkham, Samantha and Hochepied, Tino and Libert, Claude and Galor, Alon and Kim, Junho and Lodato, Michael A. and Garaycoechea, Juan, I and Gawad, Charles and West, Jay and Walsh, Christopher A. and Park, Peter J.}},
  issn         = {{1061-4036}},
  journal      = {{NATURE GENETICS}},
  keywords     = {{SIGNATURES}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1564--1571}},
  title        = {{Single-cell genome sequencing of human neurons identifies somatic point mutation and indel enrichment in regulatory elements}},
  url          = {{http://doi.org/10.1038/s41588-022-01180-2}},
  volume       = {{54}},
  year         = {{2022}},
}

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